Compositions and methods for inhibiting expression of XBP-1 gene

ABSTRACT

The invention relates to a double-stranded ribonucleic acid (dsRNA) targeting X-Box Protein 1 (XBP-1), and methods of using the dsRNA to inhibit expression of XBP-1.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. application Ser. No.12/970,189, filed on Dec. 16, 2010, which is a continuation of U.S.application Ser. No. 12/425,811, now U.S. Pat. No. 7,875,711, filed Apr.17, 2009, which claims priority to U.S. Application Ser. No. 61/045,947,filed Apr. 17, 2008, U.S. Ser. No. 61/078,302, filed Jul. 3, 2008, andU.S. Ser. No. 61/081,861, filed Jul. 18, 2008, which are herebyincorporated by reference in their entirety.

SEQUENCE LISTING

The instant application contains a Sequence Listing which has beensubmitted in ASCII format via EFS-Web and is hereby incorporated byreference in its entirety. Said ASCII copy, created on Sep. 14, 2012, isnamed 21586US_CRF_sequencelisting.txt and is 1, 369,696 bytes in size.

FIELD OF THE INVENTION

The invention relates to a double-stranded ribonucleic acid (dsRNA)targeting X-Box Protein 1 (XBP-1), and methods of using the dsRNA toinhibit expression of XBP-1.

BACKGROUND OF THE INVENTION

X-box binding protein 1 (XBP-1) is a basic leucine zipper transcriptionfactor that is involved in the cellular unfolded protein response (UPR).XBP-1 is known to be active in the endoplasmic reticulum (ER). The ERconsists of a system of folded membranes and tubules in the cytoplasm ofcells. Proteins and lipids are manufactured and processed in the ER.When unusual demands are placed on the ER, “ER stress” occurs. ER stresscan be triggered by a viral infection, gene mutations, exposure totoxins, aggregation of improperly folded proteins or a shortage ofintracellular nutrients. The result can be Type II diabetes, metabolicsyndrome, a neurological disorder or cancer.

Two XBP-1 isoforms are known to exist in cells: spliced XBP-1S andunspliced XBP-1U. Both isoforms of XBP-1 bind to the 21-bpTax-responsive element of the human T-lymphotropic virus type 1 (HTLV-1)long terminal repeat (LTR) in vitro and transactivate HTLV-1transcription. HTLV-1 is associated with a rare form of blood dyscrasiaknown as Adult T-cell Leukemia/lymphoma (ATLL) and a myelopathy,tropical spastic paresis.

Double-stranded RNA molecules (dsRNA) have been shown to block geneexpression in a highly conserved regulatory mechanism known as RNAinterference (RNAi). WO 99/32619 (Fire et al.) disclosed the use of adsRNA of at least 25 nucleotides in length to inhibit the expression ofgenes in C. elegans. dsRNA has also been shown to degrade target RNA inother organisms, including plants (see, e.g., WO 99/53050, Waterhouse etal.; and WO 99/61631, Heifetz et al.), Drosophila (see, e.g., Yang, D.,et al., Curr. Biol. (2000) 10:1191-1200), and mammals (see WO 00/44895,Limmer; and DE 101 00 586.5, Kreutzer et al.).

SUMMARY OF THE INVENTION

The invention provides compositions containing double-strandedribonucleic acid (dsRNA) and methods for inhibiting the expression of anXBP-1 gene in a cell or mammal. The invention also provides compositionsand methods for treating pathological conditions and diseases caused bythe expression of XBP-1 gene, such as metabolic disorders (e.g.,diabetes or metabolic syndrome), cardiovascular disease, protein foldingdiseases or cancer. The dsRNAs included in the compositions featuredherein include a dsRNA having an RNA strand (the antisense strand)having a region which is less than 30 nucleotides in length, generally19-24 nucleotides in length, and is substantially complementary to atleast part of an mRNA transcript of the XBP-1 gene.

In one aspect, a dsRNA for inhibiting expression of an XBP-1 geneincludes at least two sequences that are complementary to each other.The dsRNA includes a sense strand having a first sequence and anantisense strand having a second sequence. The antisense strand includesa nucleotide sequence that is substantially complementary to at leastpart of an mRNA encoding XBP-1, and the region of complementarity isless than 30 nucleotides in length, and at least 15 nucleotides inlength. Generally, the dsRNA is 19 to 24, e.g., 19 to 21 nucleotides inlength. In some embodiments the dsRNA is from about 10 to about 15nucleotides in length, and in other embodiments the dsRNA is from about25 to about 30 nucleotides in length. The dsRNA, upon contacting with acell expressing XBP-1, inhibits the expression of an XBP-1 gene by atleast 20%, at least 25%, at least 30%, at least 35% or at least 40%,such as when assayed by a method as described herein. In one embodiment,the Factor VII dsRNA is formulated in a stable nucleic acid particle(SNALP).

For example, the dsRNA molecules featured herein can include a firstsequence of the dsRNA that is selected from the group consisting of thesense sequences of Tables 2, 4, 8, 9, 11 and 12 and a second sequencethat is selected from the group consisting of the antisense sequences ofTables 2, 4, 8, 9, 11 and 12. The dsRNA molecules featured herein caninclude naturally occurring nucleotides or can include at least onemodified nucleotide, such as a 2′-O -methyl modified nucleotide, anucleotide having a 5′-phosphorothioate group, and a terminal nucleotidelinked to a conjugate group, such as to a cholesteryl derivative, tovitamin E, or to a dodecanoic acid bisdecylamide group. Alternatively,the modified nucleotide may be chosen from the group of: a2′-deoxy-2′-fluoro modified nucleotide, a 2′-deoxy-modified nucleotide,a locked nucleotide, an a basic nucleotide, 2′-amino-modifiednucleotide, 2′-alkyl-modified nucleotide, morpholino nucleotide, aphosphoramidate, and a non-natural base comprising nucleotide.Generally, such modified sequence will be based on a first sequence ofsaid dsRNA selected from the group consisting of the sense sequences ofTables 2, 4, 8, 9, 11 and 12 and a second sequence selected from thegroup consisting of the antisense sequences of Tables 2, 4, 8, 9, 11 and12.

In one aspect, the invention provides a cell containing at least one ofthe dsRNAs featured in the invention. The cell is generally a mammaliancell, such as a human cell.

In another aspect, the invention provides a pharmaceutical compositionfor inhibiting the expression of an XBP-1 gene in an organism, generallya human subject. The composition typically includes one or more of thedsRNAs described herein and a pharmaceutically acceptable carrier ordelivery vehicle. In one embodiment, the composition is used fortreating cancer, e.g., a cancer of the liver.

In another aspect, the invention provides a method for inhibiting theexpression of an XBP-1 gene in a cell by performing the following steps:

-   -   (a) introducing into the cell a double-stranded ribonucleic acid        (dsRNA), wherein the dsRNA includes at least two sequences that        are complementary to each other. The dsRNA has a sense strand        comprising a first sequence and an antisense strand having a        second sequence; the antisense strand has a region of        complementarity that is substantially complementary to at least        a part of a mRNA encoding XBP-1, and where the region of        complementarity is less than 30 nucleotides in length, generally        19-24 nucleotides in length, and where the dsRNA, upon contact        with a cell expressing the XBP-1, inhibits expression of the        XBP-1 gene by at least 20%, at least 30%, or at least 40%;    -   and    -   (b) maintaining the cell produced in step (a) for a time        sufficient to obtain degradation of the mRNA transcript of XBP-1        gene, thereby inhibiting expression of the XBP-1 gene in the        cell.

In one embodiment, the method is for inhibiting gene expression in acell infected with HTLV-1, such as a tumor cell.

In another aspect, the invention provides methods for treating,preventing or managing pathological processes mediated by XBP-1expression, e.g., a metabolic disease such as diabetes (e.g., Type IIdiabetes or metabolic syndrome), or cardiovascular disease. The methodcan include administering to a patient in need of such treatment,prevention or management a therapeutically or prophylactically effectiveamount of one or more of the dsRNAs featured in the invention. In oneembodiment the patient has metabolic syndrome. For example, a patientwith metabolic syndrome can have one of more of high cholesterol,obesity, and/or insulin insensitivity. In some embodiments, a patientwith metabolic syndrome will also have heart disease. In anotherembodiment, the patient has a dyslipidemia or a disorder associated witha dyslipidemia. For example, in one embodiment the patient hasatherosclerosis, which is often associated with hypercholesterolemia. Inanother embodiment, the patient has cancer or a neurological disorder.In yet another embodiment, the patient (e.g., a human patient) isinfected with a retrovirus, such as HTLV-1. In another embodiment, thepatient has a disorder or condition caused by the HTVL-1, such as amyelopathy, e.g., tropical spastic paresis. In one embodiment,administration of the dsRNA targeting XBP-1 alleviates or relieves theseverity of at least one symptom of the XBP-1 mediated disorder in thepatient.

In another embodiment, the invention provides a vector for inhibitingthe expression of an XBP-1 gene in a cell. In one embodiment, the vectorincludes at least one regulatory sequence operably linked to anucleotide sequence that encodes at least one strand of one of a dsRNAfeatured in the invention.

In another embodiment, the invention provides a cell containing a vectorfor inhibiting the expression of an XBP-1 gene in a cell. The vectorincludes a regulatory sequence operably linked to a nucleotide sequencethat encodes at least one strand of one of the dsRNA featured in theinvention.

In a further embodiment, the invention provides a composition containingan XBP-1 dsRNA, in combination with a second dsRNA targeting a secondgene involved in a pathological disease, and useful for treating thedisease, e.g., diabetes or cardiovascular disease.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A and 1B represent the sequence of the XBP-1 5′ RACE productaround the target sequence of the siRNA AD18038. The intended cleavagesite of the siRNA is indicated by a vertical arrow above the sequence.The cleavage sites due to degradation of the 5′ RACE product in mice areindicated by arrowheads above the sequence. “0/22” is the number ofcleavage events what were observed at the expected XBP-1 siRNA cleavagesite in the sample group of negative control mice, which were treatedwith siRNA LNP01-1955 or PBS (FIG. 1A; SEQ ID NO:4329). “26/34” is thenumber of cleavage events that were observed at the expected siRNAcleavage site in the sample group of mice treated with the XBP-1 siRNAAD18038 (FIG. 1B; SEQ ID NO:4330). The underlined sequence is the targetof the XBP-1 siRNA AD18038.

FIG. 2 is the sequence of human XBP-1 mRNA as recorded at RefSeq No.NM_(—)005080.2 (GI Ref. No. 14110394) (SEQ ID NO:4331).

FIG. 3 is the sequence of mouse XBP-1 mRNA as recorded at RefSeq No.NM_(—)013842.2 (GI Ref. No. 13775155) (SEQ ID NO:4332). The underlinedsequence is the target of siRNA AD18038.

FIG. 4 is the sequence of rat XBP-1 mRNA as recorded at RefSeq No.NM_(—)001004210.1 (GI Ref. No. 51948391) (SEQ ID NO:4333).

FIG. 5 is the sequence of rhesus XBP-1 as recorded at RefSeq No.XM_(—)001103095.1 (GI Ref. No. 109093732) (SEQ ID NO:4334).

FIG. 6 illustrates mXBP-1 and cholesterol levels after XBP-1 siRNAinjection in C57BL/6 mice.

DETAILED DESCRIPTION OF THE INVENTION

The invention provides dsRNAs and methods of using the dsRNAs forinhibiting the expression of an XBP-1 gene in a cell or a mammal wherethe dsRNA targets the XBP-1 gene. The invention also providescompositions and methods for treating pathological conditions anddiseases, such as a metabolic disease or a cardiovascular disease, in amammal caused by the expression of the XBP-1 gene. dsRNA directs thesequence-specific degradation of mRNA through a process known as RNAinterference (RNAi).

The dsRNAs of the compositions featured herein include an RNA strand(the antisense strand) having a region which is less than 30 nucleotidesin length, generally 19-24 nucleotides in length, and is substantiallycomplementary to at least part of an mRNA transcript of the XBP-1 gene.The use of these dsRNAs enables the targeted degradation of mRNAs ofgenes that are implicated in replication and or maintenance of cancercells in mammals. Very low dosages of XBP-1 dsRNAs in particular canspecifically and efficiently mediate RNAi, resulting in significantinhibition of expression of the XBP-1 gene. The methods and compositionscontaining the XBP-1 dsRNA are useful for treating pathologicalprocesses mediated by XBP-1 expression, e.g., a metabolic disease orcardiovascular disease.

The following detailed description discloses how to make and use thecompositions containing dsRNAs to inhibit the expression of the XBP-1gene, as well as compositions and methods for treating diseases anddisorders caused by the expression of these genes, such as leukemia. Thepharmaceutical compositions featured in the invention include a dsRNAhaving an antisense strand comprising a region of complementarity whichis less than 30 nucleotides in length, generally 19-24 nucleotides inlength, and is substantially complementary to at least part of an RNAtranscript of the XBP-1 gene, together with a pharmaceuticallyacceptable carrier. The compositions featured in the invention alsoinclude a dsRNA having an antisense strand having a region ofcomplementarity which is less than 30 nucleotides in length, generally19-24 nucleotides in length, and is substantially complementary to atleast part of an RNA transcript of the XBP-1 gene.

Accordingly, in some aspects, pharmaceutical compositions containing theXBP-1 dsRNA and a pharmaceutically acceptable carrier, methods of usingthe compositions to inhibit expression of the XBP-1 gene, and methods ofusing the pharmaceutical compositions to treat diseases caused byexpression of the XBP-1 gene are featured in the invention.

I. Definitions

For convenience, the meaning of certain terms and phrases used in thespecification, examples, and appended claims, are provided below. Ifthere is an apparent discrepancy between the usage of a term in otherparts of this specification and its definition provided in this section,the definition in this section shall prevail.

“G,” “C,” “A,” “T” and “U” each generally stand for a nucleotide thatcontains guanine, cytosine, adenine, thymidine and uracil as a base,respectively. However, it will be understood that the term“ribonucleotide” or “nucleotide” can also refer to a modifiednucleotide, as further detailed below, or a surrogate replacementmoiety. The skilled person is well aware that guanine, cytosine,adenine, thymidine and uracil may be replaced by other moieties withoutsubstantially altering the base pairing properties of an oligonucleotidecomprising a nucleotide bearing such replacement moiety. For example,without limitation, a nucleotide comprising inosine as its base may basepair with nucleotides containing adenine, cytosine, or uracil. Hence,nucleotides containing uracil, guanine, or adenine may be replaced inthe nucleotide sequences of dsRNA featured in the invention by anucleotide containing, for example, inosine. In another example, adenineand cytosine anywhere in the oligonucleotide can be replaced withguanine and uracil, respectively to form G:U Wobble base pairing withthe target mRNA. Sequences containing such replacement moieties aresuitable for the compositions and methods featured the invention.

As used herein, “XBP-1” refers to X-Box Protein 1, which is also knownas Tax-responsive element-binding protein 5, TREB5, and XBP2. XBP-1sequence can be found as NCBI GeneID:7494 and RefSeq IDnumber:NM_(—)005080 (human) (FIG. 1) and NM_(—)013842 (mouse, FIG. 2). AdsRNA featured in the invention can target a specific XBP-1 isoform,e.g., the spliced form (XBP-1S) or the unspliced form (XBP-1U), or adsRNA featured in the invention can target both isoforms by binding to acommon region of the mRNA transcript.

As used herein, “target sequence” refers to a contiguous portion of thenucleotide sequence of an mRNA molecule formed during the transcriptionof the XBP-1 gene, including mRNA that is a product of RNA processing ofa primary transcription product.

As used herein, the term “strand comprising a sequence” refers to anoligonucleotide comprising a chain of nucleotides that is described bythe sequence referred to using the standard nucleotide nomenclature.

As used herein, and unless otherwise indicated, the term“complementary,” when used to describe a first nucleotide sequence inrelation to a second nucleotide sequence, refers to the ability of anoligonucleotide or polynucleotide comprising the first nucleotidesequence to hybridize and form a duplex structure under certainconditions with an oligonucleotide or polynucleotide comprising thesecond nucleotide sequence, as will be understood by the skilled person.Such conditions can, for example, be stringent conditions, wherestringent conditions may include: 400 mM NaCl, 40 mM PIPES pH 6.4, 1 mMEDTA, 50° C. or 70° C. for 12-16 hours followed by washing. Otherconditions, such as physiologically relevant conditions as may beencountered inside an organism, can apply. The skilled person will beable to determine the set of conditions most appropriate for a test ofcomplementarity of two sequences in accordance with the ultimateapplication of the hybridized nucleotides.

This includes base-pairing of the oligonucleotide or polynucleotidecomprising the first nucleotide sequence to the oligonucleotide orpolynucleotide comprising the second nucleotide sequence over the entirelength of the first and second nucleotide sequence. Such sequences canbe referred to as “fully complementary” with respect to each otherherein. However, where a first sequence is referred to as “substantiallycomplementary” with respect to a second sequence herein, the twosequences can be fully complementary, or they may form one or more, butgenerally not more than 4, 3 or 2 mismatched base pairs uponhybridization, while retaining the ability to hybridize under theconditions most relevant to their ultimate application. However, wheretwo oligonucleotides are designed to form, upon hybridization, one ormore single stranded overhangs, such overhangs shall not be regarded asmismatches with regard to the determination of complementarity. Forexample, a dsRNA comprising one oligonucleotide 21 nucleotides in lengthand another oligonucleotide 23 nucleotides in length, wherein the longeroligonucleotide comprises a sequence of 21 nucleotides that is fullycomplementary to the shorter oligonucleotide, may yet be referred to as“fully complementary” for the purposes described herein.

“Complementary” sequences, as used herein, may also include, or beformed entirely from, non-Watson-Crick base pairs and/or base pairsformed from non-natural and modified nucleotides, in as far as the aboverequirements with respect to their ability to hybridize are fulfilled.Such non-Watson-Crick base pairs includes, but not limited to, G:UWobble or Hoogstein base pairing.

The terms “complementary,” “fully complementary” and “substantiallycomplementary” herein may be used with respect to the base matchingbetween the sense strand and the antisense strand of a dsRNA, or betweenthe antisense strand of a dsRNA and a target sequence, as will beunderstood from the context of their use.

As used herein, a polynucleotide which is “substantially complementaryto at least part of” a messenger RNA (mRNA) refers to a polynucleotidewhich is substantially complementary to a contiguous portion of the mRNAof interest (e.g., encoding XBP-1). For example, a polynucleotide iscomplementary to at least a part of an XBP-1 mRNA if the sequence issubstantially complementary to a non-interrupted portion of an mRNAencoding XBP-1.

The term “double-stranded RNA” or “dsRNA,” as used herein, refers to acomplex of ribonucleic acid molecules, having a duplex structurecomprising two anti-parallel and substantially complementary, as definedabove, nucleic acid strands. The two strands forming the duplexstructure may be different portions of one larger RNA molecule, or theymay be separate RNA molecules. Where the two strands are part of onelarger molecule, and therefore are connected by an uninterrupted chainof nucleotides between the 3′-end of one strand and the 5′ end of therespective other strand forming the duplex structure, the connecting RNAchain is referred to as a “hairpin loop.” Where the two strands areconnected covalently by means other than an uninterrupted chain ofnucleotides between the 3′-end of one strand and the 5′ end of therespective other strand forming the duplex structure, the connectingstructure is referred to as a “linker.” The RNA strands may have thesame or a different number of nucleotides. The maximum number of basepairs is the number of nucleotides in the shortest strand of the dsRNAminus any overhangs that are present in the duplex. In addition to theduplex structure, a dsRNA may comprise one or more nucleotide overhangs.For example, a dsRNA can have a dinucleotide overhang at the 3′ end atone or both of the sense or antisense strands, such as a dTdT(deoxythymidine-deoxythymidine) or a dTsdT(deoxythymidine-(thiophosphate linker)-deoxythymidine) dinucleotideoverhang at one or both of the 3′ ends of the sense or antisensestrands.

As used herein, a “nucleotide overhang” refers to the unpairednucleotide or nucleotides that protrude from the duplex structure of adsRNA when a 3′-end of one strand of the dsRNA extends beyond the 5′-endof the other strand, or vice versa. “Blunt” or “blunt end” means thatthere are no unpaired nucleotides at that end of the dsRNA, i.e., nonucleotide overhang. A “blunt ended” dsRNA is a dsRNA that isdouble-stranded over its entire length, i.e., no nucleotide overhang ateither end of the molecule.

The term “antisense strand” refers to the strand of a dsRNA whichincludes a region that is substantially complementary to a targetsequence. As used herein, the term “region of complementarity” refers tothe region on the antisense strand that is substantially complementaryto a sequence, for example a target sequence, as defined herein. Wherethe region of complementarity is not fully complementary to the targetsequence, the mismatches may be in the internal or terminal regions ofthe molecule. Generally, the most tolerated mismatches are in theterminal regions, e.g., within 6, 5, 4, 3, or 2 nucleotides of the 5′and/or 3′ terminus.

The term “sense strand,” as used herein, refers to the strand of a dsRNAthat includes a region that is substantially complementary to a regionof the antisense strand.

The term “identity” is the relationship between two or morepolynucleotide sequences, as determined by comparing the sequences.Identity also means the degree of sequence relatedness betweenpolynucleotide sequences, as determined by the match between strings ofsuch sequences. While there exist a number of methods to measureidentity between two polynucleotide sequences, the term is well known toskilled artisans (see, e.g., Sequence Analysis in Molecular Biology, vonHeinje, G., Academic Press (1987); and Sequence Analysis Primer,Gribskov., M. and Devereux, J., eds., M. Stockton Press, New York(1991)). “Substantially identical,” as used herein, means there is avery high degree of homology (e.g., 100% sequence identity) between thesense strand of the dsRNA and the corresponding part of the target gene.However, dsRNA having greater than 90%, or 95% sequence identity may beused in the present invention, and thus sequence variations that mightbe expected due to genetic mutation, strain polymorphism, orevolutionary divergence can be tolerated. The dsRNA is typically 100%complementary to the target RNA, but in some embodiments, the dsRNA maycontain single or multiple base-pair random mismatches between the RNAand the target gene.

As used herein, the term “SNALP” refers to a stable nucleic acid-lipidparticle. A SNALP represents a vesicle of lipids coating a reducedaqueous interior comprising a nucleic acid such as an iRNA agent or aplasmid from which an iRNA agent is transcribed. SNALPs are described,e.g., in U.S. Patent Application Publication Nos. 20060240093,20070135372, and U.S. Ser. No. 61/045,228 filed Apr. 15, 2008. Theseapplications are hereby incorporated by reference.

“Introducing into a cell,” when referring to a dsRNA, means facilitatinguptake or absorption into the cell, as is understood by those skilled inthe art. Absorption or uptake of dsRNA can occur through unaideddiffusive or active cellular processes, or by auxiliary agents ordevices. The meaning of this term is not limited to cells in vitro; adsRNA may also be “introduced into a cell,” wherein the cell is part ofa living organism. In such instance, introduction into the cell willinclude the delivery to the organism. For example, for in vivo delivery,dsRNA can be injected into a tissue site or administered systemically.In vivo delivery can also be by a beta-glucan delivery system, such asthose described in U.S. Pat. Nos. 5,032,401 and 5,607,677, and U.S.Publication No. 2005/0281781. U.S. Pat. Nos. 5,032,401 and 5,607,677,and U.S. Publication No. 2005/0281781 are hereby incorporated byreference in their entirety. In vitro introduction into a cell includesmethods known in the art such as electroporation and lipofection.

The terms “silence,” “inhibit the expression of,” “down-regulate theexpression of,” “suppress the expression of,” and the like, in as far asthey refer to the XBP-1 gene, herein refer to the at least partialsuppression of the expression of the XBP-1 gene, as manifested by areduction of the amount of XBP-1 mRNA which may be isolated from a firstcell or group of cells in which the XBP-1 gene is transcribed and whichhas or have been treated such that the expression of the XBP-1 gene isinhibited, as compared to a second cell or group of cells substantiallyidentical to the first cell or group of cells but which has or have notbeen so treated (control cells). The degree of inhibition is usuallyexpressed in terms of

${\frac{\left( {{mRNA}\mspace{14mu}{in}\mspace{14mu}{control}\mspace{14mu}{cells}} \right) - \left( {{mRNA}\mspace{14mu}{in}\mspace{14mu}{treated}\mspace{14mu}{cells}} \right)}{\left( {{mRNA}\mspace{20mu}{in}\mspace{20mu}{control}\mspace{20mu}{cells}} \right)} \cdot 100}\;\%$

Alternatively, the degree of inhibition may be given in terms of areduction of a parameter that is functionally linked to XBP-1 geneexpression, e.g., the amount of protein encoded by the XBP-1 gene whichis secreted by a cell, or the number of cells displaying a certainphenotype, e.g., apoptosis. In principle, XBP-1 gene silencing may bedetermined in any cell expressing XBP-1, either constitutively or bygenomic engineering, and by any appropriate assay. However, when areference is needed in order to determine whether a given dsRNA inhibitsthe expression of the XBP-1 gene by a certain degree and therefore isencompassed by the instant invention, the assay provided in the Examplesbelow shall serve as such reference.

For example, in certain instances, expression of the XBP-1 gene issuppressed by at least about 20%, 25%, 30%, 35%, 40%, 45%, or 50% byadministration of the double-stranded oligonucleotide featured in theinvention. In some embodiments, the XBP-1 gene is suppressed by at leastabout 60%, 70%, or 80% by administration of the double-strandedoligonucleotide featured in the invention. In some embodiments, theXBP-1 gene is suppressed by at least about 85%, 90%, or 95% byadministration of the double-stranded oligonucleotide featured in theinvention.

As used herein in the context of XBP-1 expression, the terms “treat,”“treatment,” and the like, refer to relief from or alleviation ofpathological processes mediated by XBP-1 expression. In the context ofthe present invention insofar as it relates to any of the otherconditions recited herein below (other than pathological processesmediated by XBP-1 expression), the terms “treat,” “treatment,” and thelike mean to relieve or alleviate at least one symptom associated withsuch condition, or to slow or reverse the progression of such condition,such as the slowing and progression of hepatic carcinoma.

As used herein, the phrases “therapeutically effective amount” and“prophylactically effective amount” refer to an amount that provides atherapeutic benefit in the treatment, prevention, or management ofpathological processes mediated by XBP-1 expression or an overt symptomof pathological processes mediated by XBP-1 expression. The specificamount that is therapeutically effective can be readily determined by anordinary medical practitioner, and may vary depending on factors knownin the art, such as, e.g., the type of pathological processes mediatedby XBP-1 expression, the patient's history and age, the stage ofpathological processes mediated by XBP-1 expression, and theadministration of other anti-pathological processes mediated by XBP-1expression agents.

As used herein, a “pharmaceutical composition” comprises apharmacologically effective amount of a dsRNA and a pharmaceuticallyacceptable carrier. As used herein, “pharmacologically effectiveamount,” “therapeutically effective amount” or simply “effective amount”refers to that amount of an RNA effective to produce the intendedpharmacological, therapeutic or preventive result. For example, if agiven clinical treatment is considered effective when there is at leasta 25% reduction in a measurable parameter associated with a disease ordisorder, a therapeutically effective amount of a drug for the treatmentof that disease or disorder is the amount necessary to effect at least a25% reduction in that parameter.

The term “pharmaceutically acceptable carrier” refers to a carrier foradministration of a therapeutic agent. Such carriers include, but arenot limited to, saline, buffered saline, dextrose, water, glycerol,ethanol, and combinations thereof. The term specifically excludes cellculture medium. For drugs administered orally, pharmaceuticallyacceptable carriers include, but are not limited to pharmaceuticallyacceptable excipients such as inert diluents, disintegrating agents,binding agents, lubricating agents, sweetening agents, flavoring agents,coloring agents and preservatives. Suitable inert diluents includesodium and calcium carbonate, sodium and calcium phosphate, and lactose,while corn starch and alginic acid are suitable disintegrating agents.Binding agents may include starch and gelatin, while the lubricatingagent, if present, will generally be magnesium stearate, stearic acid ortalc. If desired, the tablets may be coated with a material such asglyceryl monostearate or glyceryl distearate, to delay absorption in thegastrointestinal tract.

As used herein, a “transformed cell” is a cell into which a vector hasbeen introduced from which a dsRNA molecule may be expressed.

II. Double-Stranded Ribonucleic Acid (dsRNA)

In one embodiment, the invention provides double-stranded ribonucleicacid (dsRNA) molecules for inhibiting the expression of an XBP-1 gene ina cell or mammal, e.g., in a human having a metabolic disease, such asdiabetes, or cardiovascular disease, where the dsRNA includes anantisense strand having a region of complementarity which iscomplementary to at least a part of an mRNA formed in the expression ofthe XBP-1 gene, and where the region of complementarity is less than 30nucleotides in length, generally 19-24 nucleotides in length, and wheresaid dsRNA, upon contact with a cell expressing said XBP-1 gene,inhibits the expression of said XBP-1 gene by at least 30% as assayedby, for example, a PCR or branched DNA (bDNA) based method. The dsRNAincludes two RNA strands that are sufficiently complementary tohybridize to form a duplex structure. One strand of the dsRNA (theantisense strand) includes a region of complementarity that issubstantially complementary, and generally fully complementary, to atarget sequence, derived from the sequence of an mRNA formed during theexpression of the XBP-1 gene, the other strand (the sense strand)includes a region that is complementary to the antisense strand, suchthat the two strands hybridize and form a duplex structure when combinedunder suitable conditions. Generally, the duplex structure is between 15and 30, more generally between 18 and 25, yet more generally between 19and 24, and most generally between 19 and 21 base pairs in length.Similarly, the region of complementarity to the target sequence isbetween 15 and 30, more generally between 18 and 25, yet more generallybetween 19 and 24, and most generally between 19 and 21 nucleotides inlength. In some embodiments, the dsRNA is between 10 and 15 nucleotidesin length, and in other embodiments, the dsRNA is between 25 and 30nucleotides in length. The dsRNA featured in the invention may furtherinclude one or more single-stranded nucleotide overhangs.

The dsRNA can be synthesized by standard methods known in the art asfurther discussed below, e.g., by use of an automated DNA synthesizer,such as are commercially available from, for example, Biosearch, AppliedBiosystems, Inc. In one embodiment, the XBP-1 gene is the human XBP-1gene. In specific embodiments, the first sequence is selected from thegroup consisting of the sense sequences of Tables 2, 4, 8, 9, 11 and 12,and the second sequence is selected from the group consisting of theantisense sequences of Tables 2, 4, 8, 9, 11 and 12. Alternativeantisense agents that target elsewhere in the target sequence providedin Tables 2, 4, 8, 9, 11 and 12 can readily be determined using thetarget sequence and the flanking XBP-1 sequence.

The dsRNA will include at least two nucleotide sequence selected fromthe groups of sequences provided in Tables 2, 4, 8, 9, 11 and 12. One ofthe two sequences is complementary to the other of the two sequences,with one of the sequences being substantially complementary to asequence of an mRNA generated in the expression of the XBP-1 gene. Assuch, the dsRNA will include two oligonucleotides, where oneoligonucleotide is described as the sense strand in Tables 2, 4, 8, 9,11 and 12 and the second oligonucleotide is described as the antisensestrand in Tables 2, 4, 8, 9, 11 and 12.

The skilled person is well aware that dsRNAs comprising a duplexstructure of between 20 and 23, but specifically 21, base pairs havebeen hailed as particularly effective in inducing RNA interference(Elbashir et al., EMBO 2001, 20:6877-6888). However, others have foundthat shorter or longer dsRNAs can be effective as well. In theembodiments described above, by virtue of the nature of theoligonucleotide sequences provided in Tables 2, 4, 8, 9, 11 and 12, thedsRNAs featured in the invention can include at least one strand of alength of minimally 21 nt. It can be reasonably expected that shorterdsRNAs having one of the sequences of Tables 2, 4, 8, 9, 11 and 12 minusonly a few nucleotides on one or both ends may be similarly effective ascompared to the dsRNAs described above. Hence, dsRNAs having a partialsequence of at least 15, 16, 17, 18, 19, 20, or more contiguousnucleotides from one of the sequences of Tables 2, 4, 8, 9, 11 and 12,and differing in their ability to inhibit the expression of the XBP-1gene in a FACS assay as described herein below by not more than 5, 10,15, 20, 25, or 30% inhibition from a dsRNA comprising the full sequence,are contemplated by the invention. Further, dsRNAs that cleave within adesired XBP-1 target sequence can readily be made using thecorresponding XBP-1 antisense sequence and a complementary sensesequence.

In addition, the dsRNAs provided in 2, 4, 8, 9, 11 and 12 identify asite in the XBP-1 mRNA that is susceptible to RNAi based cleavage. Assuch the present invention further features dsRNAs that target withinthe sequence targeted by one of the agents of the present invention. Asused herein a second dsRNA is said to target within the sequence of afirst dsRNA if the second dsRNA cleaves the message anywhere within themRNA that is complementary to the antisense strand of the first dsRNA.Such a second dsRNA will generally consist of at least 15 contiguousnucleotides from one of the sequences provided in Tables 2, 4, 8, 9, 11and 12 coupled to additional nucleotide sequences taken from the regioncontiguous to the selected sequence in the XBP-1 gene. For example, thelast 15 nucleotides of SEQ ID NO:1 combined with the next sixnucleotides from the target XBP-1 gene produces a single strand agent of21 nucleotides that is based on one of the sequences provided in Tables2, 4, 8, 9, 11 and 12.

The dsRNA featured in the invention can contain one or more mismatchesto the target sequence. In one embodiment, the dsRNA featured theinvention contains no more than 3 mismatches. If the antisense strand ofthe dsRNA contains mismatches to a target sequence, it the area ofmismatch is typically not located in the center of the region ofcomplementarity. If the antisense strand of the dsRNA containsmismatches to the target sequence, the mismatch is typically restrictedto 5 nucleotides from either end, for example 5, 4, 3, 2, or 1nucleotide from either the 5′ or 3′ end of the region ofcomplementarity. For example, for a 23 nucleotide dsRNA strand which iscomplementary to a region of the XBP-1 gene, the dsRNA generally doesnot contain any mismatch within the central 13 nucleotides. The methodsdescribed within the invention can be used to determine whether a dsRNAcontaining a mismatch to a target sequence is effective in inhibitingthe expression of the XBP-1 gene. Consideration of the efficacy ofdsRNAs with mismatches in inhibiting expression of the XBP-1 gene isimportant, especially if the particular region of complementarity in theXBP-1 gene is known to have polymorphic sequence variation within thepopulation.

In one embodiment, at least one end of the dsRNA has a single-strandednucleotide overhang of 1 to 4, generally 1 or 2 nucleotides. dsRNAshaving at least one nucleotide overhang have unexpectedly superiorinhibitory properties than their blunt-ended counterparts. Moreover, thepresent inventors have discovered that the presence of only onenucleotide overhang strengthens the interference activity of the dsRNA,without affecting its overall stability. dsRNA having only one overhanghas proven particularly stable and effective in vivo, as well as in avariety of cells, cell culture mediums, blood, and serum. Generally, thesingle-stranded overhang is located at the 3′-terminal end of theantisense strand or, alternatively, at the 3′-terminal end of the sensestrand. The dsRNA may also have a blunt end, generally located at the5′-end of the antisense strand. Such dsRNAs have improved stability andinhibitory activity, thus allowing administration at low dosages, i.e.,less than 5 mg/kg body weight of the recipient per day. In oneembodiment, the antisense strand of the dsRNA has a 1-10 nucleotideoverhang at the 3′ end and/or the 5′ end. In one embodiment, the sensestrand of the dsRNA has a 1-10 nucleotide overhang at the 3′ end and/orthe 5′ end. In another embodiment, one or more of the nucleotides in theoverhang is replaced with a nucleoside thiophosphate.

In yet another embodiment, the dsRNA is chemically modified to enhancestability. The nucleic acids featured in the invention may besynthesized and/or modified by methods well established in the art, suchas those described in “Current protocols in nucleic acid chemistry,”Beaucage, S. L. et al. (Edrs.), John Wiley & Sons, Inc., New York, N.Y.,USA, which is hereby incorporated herein by reference. Specific examplesof dsRNA compounds useful in this invention include dsRNAs containingmodified backbones or no natural internucleoside linkages. As defined inthis specification, dsRNAs having modified backbones include those thatretain a phosphorus atom in the backbone and those that do not have aphosphorus atom in the backbone. For the purposes of this specification,and as sometimes referenced in the art, modified dsRNAs that do not havea phosphorus atom in their internucleoside backbone can also beconsidered to be oligonucleosides.

Modified dsRNA backbones include, for example, phosphorothioates, chiralphosphorothioates, phosphorodithioates, phosphotriesters,aminoalkylphosphotriesters, methyl and other alkyl phosphonatesincluding 3′-alkylene phosphonates and chiral phosphonates,phosphinates, phosphoramidates including 3′-amino phosphoramidate andaminoalkylphosphoramidates, thionophosphoramidates,thionoalkylphosphonates, thionoalkylphosphotriesters, andboranophosphates having normal 3′-5′ linkages, 2′-5′ linked analogs ofthese, and those) having inverted polarity wherein the adjacent pairs ofnucleoside units are linked 3′-5′ to 5′-3′ or 2′-5′ to 5′-2′. Varioussalts, mixed salts and free acid forms are also included.

Representative U.S. patents that teach the preparation of the abovephosphorus-containing linkages include, but are not limited to, U.S.Pat. Nos. 3,687,808; 4,469,863; 4,476,301; 5,023,243; 5,177,195;5,188,897; 5,264,423; 5,276,019; 5,278,302; 5,286,717; 5,321,131;5,399,676; 5,405,939; 5,453,496; 5,455,233; 5,466,677; 5,476,925;5,519,126; 5,536,821; 5,541,316; 5,550,111; 5,563,253; 5,571,799;5,587,361; and 5,625,050, each of which is herein incorporated byreference

Modified dsRNA backbones that do not include a phosphorus atom thereinhave backbones that are formed by short chain alkyl or cycloalkylinternucleoside linkages, mixed heteroatoms and alkyl or cycloalkylinternucleoside linkages, or ore or more short chain heteroatomic orheterocyclic internucleoside linkages. These include those havingmorpholino linkages (formed in part from the sugar portion of anucleoside); siloxane backbones; sulfide, sulfoxide and sulfonebackbones; formacetyl and thioformacetyl backbones; methylene formacetyland thioformacetyl backbones; alkene containing backbones; sulfamatebackbones; methyleneimino and methylenehydrazino backbones; sulfonateand sulfonamide backbones; amide backbones; and others having mixed N,O, S and CH2 component parts.

Representative U.S. patents that teach the preparation of the aboveoligonucleosides include, but are not limited to, U.S. Pat. Nos.5,034,506; 5,166,315; 5,185,444; 5,214,134; 5,216,141; 5,235,033;5,64,562; 5,264,564; 5,405,938; 5,434,257; 5,466,677; 5,470,967;5,489,677; 5,541,307; 5,561,225; 5,596,086; 5,602,240; 5,608,046;5,610,289; 5,618,704; 5,623,070; 5,663,312; 5,633,360; 5,677,437; and,5,677,439, each of which is herein incorporated by reference.

In other suitable dsRNA mimetics, both the sugar and the internucleosidelinkage, i.e., the backbone, of the nucleotide units are replaced withnovel groups. The base units are maintained for hybridization with anappropriate nucleic acid target compound. One such oligomeric compound,an dsRNA mimetic that has been shown to have excellent hybridizationproperties, is referred to as a peptide nucleic acid (PNA). In PNAcompounds, the sugar backbone of an dsRNA is replaced with an amidecontaining backbone, in particular an aminoethylglycine backbone. Thenucleobases are retained and are bound directly or indirectly to azanitrogen atoms of the amide portion of the backbone. Representative U.S.patents that teach the preparation of PNA compounds include, but are notlimited to, U.S. Pat. Nos. 5,539,082; 5,714,331; and 5,719,262, each ofwhich is herein incorporated by reference. Further teaching of PNAcompounds can be found in Nielsen et al., Science, 1991, 254, 1497-1500.

Most embodiments featured in the invention include dsRNAs withphosphorothioate backbones and oligonucleosides with heteroatombackbones, and in particular —CH₂—NH—CH₂—, —CH₂—N(CH₃)—O—CH₂—[known as amethylene (methylimino) or MMI backbone], —CH₂—O —N(CH₃)—CH₂—,—CH₂—N(CH₃)—N(CH₃)—CH₂— and —N(CH₃)—CH₂—CH₂—[wherein the nativephosphodiester backbone is represented as —O—P—O—CH₂—] of theabove-referenced U.S. Pat. No. 5,489,677, and the amide backbones of theabove-referenced U.S. Pat. No. 5,602,240. In some embodiments, thedsRNAs featured herein have morpholino backbone structures of theabove-referenced U.S. Pat. No. 5,034,506.

Modified dsRNAs may also contain one or more substituted sugar moieties.The dsRNAs featured herein can one of the following at the 2′ position:OH; F; O-, S-, or N-alkyl; O-, S-, or N-alkenyl; O-, S- or N-alkynyl; orO-alkyl-O-alkyl, wherein the alkyl, alkenyl and alkynyl may besubstituted or unsubstituted C₁ to C₁₀ alkyl or C₂ to C₁₀ alkenyl andalkynyl. Typical modifications are O[(CH₂)_(n)O]_(m)CH₃, O(CH₂)_(n)OCH₃,O(CH₂)_(n)NH₂, O(CH₂)_(n)CH₃, O(CH₂)_(n)ONH₂, andO(CH₂)_(n)ON[(CH₂)_(n)CH₃)]₂, where n and m are from 1 to about 10. Inother embodiments, dsRNAs include one of the following at the 2′position: C₁ to C₁₀ lower alkyl, substituted lower alkyl, alkaryl,aralkyl, O-alkaryl or O-aralkyl, SH, SCH₃, OCN, Cl, Br, CN, CF₃, OCF₃,SOCH₃, SO₂CH₃, ONO₂, NO₂, N₃, NH₂, heterocycloalkyl, heterocycloalkaryl,aminoalkylamino, polyalkylamino, substituted silyl, an RNA cleavinggroup, a reporter group, an intercalator, a group for improving thepharmacokinetic properties of an dsRNA, or a group for improving thepharmacodynamic properties of an dsRNA, and other substituents havingsimilar properties. In some embodiments, the modification includes a2′-methoxyethoxy (2′-O—CH₂CH₂OCH₃, also known as 2′-O-(2-methoxyethyl)or 2′-MOE) (Martin et al., Helv. Chim. Acta, 1995, 78:486-504) i.e., analkoxy-alkoxy group. Other typical modification include2′-dimethylaminooxyethoxy, i.e., a O(CH₂)₂ON(CH₃)₂ group, also known as2′-DMAOE, as described in examples hereinbelow, and2′-dimethylaminoethoxyethoxy (also known in the art as2′-O-dimethylaminoethoxyethyl or 2′-DMAEOE), i.e.,2′-O—CH₂—O—CH₂—N(CH₂)₂, also described in examples hereinbelow.

Other modifications include 2′-methoxy (2′-OCH₃), 2′-aminopropoxy(2′-OCH₂CH₂CH₂NH₂) and 2′-fluoro (2′-F). Similar modifications may alsobe made at other positions on the dsRNA, particularly the 3′ position ofthe sugar on the 3′ terminal nucleotide or in 2′-5′ linked dsRNAs andthe 5′ position of 5′ terminal nucleotide. DsRNAs may also have sugarmimetics such as cyclobutyl moieties in place of the pentofuranosylsugar. Representative U.S. patents that teach the preparation of suchmodified sugar structures include, but are not limited to, U.S. Pat.Nos. 4,981,957; 5,118,800; 5,319,080; 5,359,044; 5,393,878; 5,446,137;5,466,786; 5,514,785; 5,519,134; 5,567,811; 5,576,427; 5,591,722;5,597,909; 5,610,300; 5,627,053; 5,639,873; 5,646,265; 5,658,873;5,670,633; and 5,700,920, certain of which are commonly owned with theinstant application, and each of which is herein incorporated byreference in its entirety.

DsRNAs may also include nucleobase (often referred to in the art simplyas “base”) modifications or substitutions. As used herein, “unmodified”or “natural” nucleobases include the purine bases adenine (A) andguanine (G), and the pyrimidine bases thymine (T), cytosine (C) anduracil (U). Modified nucleobases include other synthetic and naturalnucleobases such as 5-methylcytosine (5-me-C), 5-hydroxymethyl cytosine,xanthine, hypoxanthine, 2-aminoadenine, 6-methyl and other alkylderivatives of adenine and guanine, 2-propyl and other alkyl derivativesof adenine and guanine, 2-thiouracil, 2-thiothymine and 2-thiocytosine,5-halouracil and cytosine, 5-propynyl uracil and cytosine, 6-azo uracil,cytosine and thymine, 5-uracil (pseudouracil), 4-thiouracil, 8-halo,8-amino, 8-thiol, 8-thioalkyl, 8-hydroxyl anal other 8-substitutedadenines and guanines, 5-halo, particularly 5-bromo, 5-trifluoromethyland other 5-substituted uracils and cytosines, 7-methylguanine and7-methyladenine, 8-azaguanine and 8-azaadenine, 7-deazaguanine and7-daazaadenine and 3-deazaguanine and 3-deazaadenine. Furthernucleobases include those disclosed in U.S. Pat. No. 3,687,808, thosedisclosed in The Concise Encyclopedia Of Polymer Science AndEngineering, pages 858-859, Kroschwitz, J. L, ed. John Wiley & Sons,1990, these disclosed by Englisch et al., Angewandte Chemie,International Edition, 1991, 30, 613, and those disclosed by Sanghvi, YS., Chapter 15, DsRNA Research and Applications, pages 289-302, Crooke,S. T. and Lebleu, B., Ed., CRC Press, 1993. Certain of these nucleobasesare particularly useful for increasing the binding affinity of theoligomeric compounds featured in the invention. These include5-substituted pyrimidines, 6-azapyrimidines and N-2, N-6 and 0-6substituted purines, including 2-aminopropyladenine, 5-propynyluraciland 5-propynylcytosine. 5-methylcytosine substitutions have been shownto increase nucleic acid duplex stability by 0.6-1.2° C. (Sanghvi, Y.S., Crooke, S. T. and Lebleu, B., Eds., DsRNA Research and Applications,CRC Press, Boca Raton, 1993, pp. 276-278) and are typical basesubstitutions, particularly when combined with 2′-O-methoxyethyl sugarmodifications.

Representative U.S. patents that teach the preparation of certain of theabove noted modified nucleobases as well as other modified nucleobasesinclude, but are not limited to, the above noted U.S. Pat. No.3,687,808, as well as U.S. Pat. Nos. 4,845,205; 5,130,30; 5,134,066;5,175,273; 5,367,066; 5,432,272; 5,457,187; 5,459,255; 5,484,908;5,502,177; 5,525,711; 5,552,540; 5,587,469; 5,594,121, 5,596,091;5,614,617; and 5,681,941, each of which is herein incorporated byreference, and U.S. Pat. No. 5,750,692, also herein incorporated byreference.

Another modification of the dsRNAs featured in the invention involveschemically linking to the dsRNA one or more moieties or conjugates whichenhance the activity, cellular distribution or cellular uptake of thedsRNA. Such moieties include but are not limited to lipid moieties suchas a cholesterol moiety (Letsinger et al., Proc. Natl. Acid. Sci. USA,199, 86, 6553-6556), cholic acid (Manoharan et al., Biorg. Med. Chem.Let., 1994 4 1053-1060), a thioether, e.g., beryl-5-tritylthiol(Manoharan et al., Ann. N.Y. Acad. Sci., 1992, 660, 306-309; Manoharanet al., Biorg. Med. Chem. Let., 1993, 3, 2765-2770), a thiocholesterol(Oberhauser et al., Nucl. Acids Res., 1992, 20, 533-538), an aliphaticchain, e.g., dodecandiol or undecyl residues (Saison-Behmoaras et al.,EMBO J, 1991, 10, 1111-1118; Kabanov et al., FEBS Lett., 1990, 259,327-330; Svinarchuk et al., Biochimie, 1993, 75, 49-54), a phospholipid,e.g., di-hexadecyl-rac-glycerol or triethyl-ammonium1,2-di-O-hexadecyl-rac-glycero-3-Hphosphonate (Manoharan et al.,Tetrahedron Lett., 1995, 36, 3651-3654; Shea et al., Nucl. Acids Res.,1990, 18, 3777-3783), a polyamine or a polyethylene glycol chain(Manoharan et al., Nucleosides & Nucleotides, 1995, 14, 969-973), oradamantane acetic acid (Manoharan et al., Tetrahedron Lett., 1995, 36,3651-3654), a palmityl moiety (Mishra et al., Biochim. Biophys. Acta,1995, 1264, 229-237), or an octadecylamine orhexylamino-carbonyloxycholesterol moiety (Crooke et al., J. Pharmacol.Exp. Ther., 1996, 277, 923-937).

Representative U.S. patents that teach the preparation of such dsRNAconjugates include, but are not limited to, U.S. Pat. Nos. 4,828,979;4,948,882; 5,218,105; 5,525,465; 5,541,313; 5,545,730; 5,552,538;5,578,717, 5,580,731; 5,591,584; 5,109,124; 5,118,802; 5,138,045;5,414,077; 5,486,603; 5,512,439; 5,578,718; 5,608,046; 4,587,044;4,605,735; 4,667,025; 4,762,779; 4,789,737; 4,824,941; 4,835,263;4,876,335; 4,904,582; 4,958,013; 5,082,830; 5,112,963; 5,214,136;5,082,830; 5,112,963; 5,214,136; 5,245,022; 5,254,469; 5,258,506;5,262,536; 5,272,250; 5,292,873; 5,317,098; 5,371,241, 5,391,723;5,416,203, 5,451,463; 5,510,475; 5,512,667; 5,514,785; 5,565,552;5,567,810; 5,574,142; 5,585,481; 5,587,371; 5,595,726; 5,597,696;5,599,923; 5,599,928 and 5,688,941, each of which is herein incorporatedby reference.

It is not necessary for all positions in a given compound to beuniformly modified, and in fact more than one of the aforementionedmodifications may be incorporated in a single compound or even at asingle nucleoside within an dsRNA. The present invention also includesdsRNA compounds which are chimeric compounds. “Chimeric” dsRNA compoundsor “chimeras,” in the context of this invention, are dsRNA compounds,particularly dsRNAs, which contain two or more chemically distinctregions, each made up of at least one monomer unit, i.e., a nucleotidein the case of an dsRNA compound. These dsRNAs typically contain atleast one region wherein the dsRNA is modified so as to confer upon thedsRNA increased resistance to nuclease degradation, increased cellularuptake, and/or increased binding affinity for the target nucleic acid.An additional region of the dsRNA may serve as a substrate for enzymescapable of cleaving RNA:DNA or RNA:RNA hybrids. By way of example, RNaseH is a cellular endonuclease which cleaves the RNA strand of anRNA:DNAduplex. Activation of RNase H, therefore, results in cleavage ofthe RNA target, thereby greatly enhancing the efficiency of dsRNAinhibition of gene expression. Consequently, comparable results canoften be obtained with shorter dsRNAs when chimeric dsRNAs are used,compared to phosphorothioate deoxydsRNAs hybridizing to the same targetregion. Cleavage of the RNA target can be routinely detected by gelelectrophoresis and, if necessary, associated nucleic acid hybridizationtechniques known in the art.

In certain instances, the dsRNA may be modified by a non-ligand group. Anumber of non-ligand molecules have been conjugated to dsRNAs in orderto enhance the activity, cellular distribution or cellular uptake of thedsRNA, and procedures for performing such conjugations are available inthe scientific literature. Such non-ligand moieties have included lipidmoieties, such as cholesterol (Letsinger et al., Proc. Natl. Acad. Sci.USA, 1989, 86:6553), cholic acid (Manoharan et al., Bioorg. Med. Chem.Lett., 1994, 4:1053), a thioether, e.g., hexyl-5-tritylthiol (Manoharanet al., Ann. N.Y. Acad. Sci., 1992, 660:306; Manoharan et al., Bioorg.Med. Chem. Let., 1993, 3:2765), a thiocholesterol (Oberhauser et al.,Nucl. Acids Res., 1992, 20:533), an aliphatic chain, e.g., dodecandiolor undecyl residues (Saison-Behmoaras et al., EMBO J., 1991, 10:111;Kabanov et al., FEBS Lett., 1990, 259:327; Svinarchuk et al., Biochimie,1993, 75:49), a phospholipid, e.g., di-hexadecyl-rac-glycerol ortriethylammonium 1,2-di-O-hexadecyl-rac-glycero-3-H-phosphonate(Manoharan et al., Tetrahedron Lett., 1995, 36:3651; Shea et al., Nucl.Acids Res., 1990, 18:3777), a polyamine or a polyethylene glycol chain(Manoharan et al., Nucleosides & Nucleotides, 1995, 14:969), oradamantane acetic acid (Manoharan et al., Tetrahedron Lett., 1995,36:3651), a palmityl moiety (Mishra et al., Biochim. Biophys. Acta,1995, 1264:229), or an octadecylamine orhexylamino-carbonyl-oxycholesterol moiety (Crooke et al., J. Pharmacol.Exp. Ther., 1996, 277:923). Representative United States patents thatteach the preparation of such dsRNA conjugates have been listed above.Typical conjugation protocols involve the synthesis of dsRNAs bearing anaminolinker at one or more positions of the sequence. The amino group isthen reacted with the molecule being conjugated using appropriatecoupling or activating reagents. The conjugation reaction may beperformed either with the dsRNA still bound to the solid support orfollowing cleavage of the dsRNA in solution phase. Purification of thedsRNA conjugate by HPLC typically affords the pure conjugate.

Vector Encoded dsRNAs

In another aspect, XBP-1 specific dsRNA molecules are expressed fromtranscription units inserted into DNA or RNA vectors (see, e.g.,Couture, A, et al., TIG. (1996), 12:5-10; Skillern, A., et al.,International PCT Publication No. WO 00/22113, Conrad, International PCTPublication No. WO 00/22114, and Conrad, U.S. Pat. No. 6,054,299). Thesetransgenes can be introduced as a linear construct, a circular plasmid,or a viral vector, which can be incorporated and inherited as atransgene integrated into the host genome. The transgene can also beconstructed to permit it to be inherited as an extrachromosomal plasmid(Gassmann, et al., Proc. Natl. Acad. Sci. USA (1995) 92:1292).

The individual strands of a dsRNA can be transcribed by promoters on twoseparate expression vectors and co-transfected into a target cell.Alternatively each individual strand of the dsRNA can be transcribed bypromoters both of which are located on the same expression plasmid. Inone embodiment, a dsRNA is expressed as an inverted repeat joined by alinker polynucleotide sequence such that the dsRNA has a stem and loopstructure.

The recombinant dsRNA expression vectors are generally DNA plasmids orviral vectors. dsRNA expressing viral vectors can be constructed basedon, but not limited to, adeno-associated virus (for a review, seeMuzyczka, et al., Curr. Topics Micro. Immunol. (1992) 158:97-129));adenovirus (see, for example, Berkner, et al., BioTechniques (1998)6:616), Rosenfeld et al. (1991, Science 252:431-434), and Rosenfeld etal. (1992), Cell 68:143-155)); or alphavirus as well as others known inthe art. Retroviruses have been used to introduce a variety of genesinto many different cell types, including epithelial cells, in vitroand/or in vivo (see, e.g., Eglitis, et al., Science (1985)230:1395-1398; Danos and Mulligan, Proc. Natl Acad. Sci. USA (1998)85:6460-6464; Wilson et al., 1988, Proc. Natl. Acad. Sci. USA85:3014-3018; Armentano et al., 1990, Proc. Natl. Acad. Sci. USA87:61416145; Huber et al., 1991, Proc. Natl. Acad. Sci. USA88:8039-8043; Ferry et al., 1991, Proc. Natl. Acad. Sci. USA88:8377-8381; Chowdhury et al., 1991, Science 254:1802-1805; vanBeusechem. et al., 1992, Proc. Nad. Acad. Sci. USA 89:7640-19; Kay etal., 1992, Human Gene Therapy 3:641-647; Dai et al., 1992, Proc.Natl.Acad. Sci. USA 89:10892-10895; Hwu et al., 1993, J. Immunol.150:4104-4115; U.S. Pat. Nos. 4,868,116; 4,980,286; PCT Application WO89/07136; PCT Application WO 89/02468; PCT Application WO 89/05345; andPCT Application WO 92/07573). Recombinant retroviral vectors capable oftransducing and expressing genes inserted into the genome of a cell canbe produced by transfecting the recombinant retroviral genome intosuitable packaging cell lines such as PA317 and Psi-CRIP (Comette etal., 1991, Human Gene Therapy 2:5-10; Cone et al., 1984, Proc. Natl.Acad. Sci. USA 81:6349). Recombinant adenoviral vectors can be used toinfect a wide variety of cells and tissues in susceptible hosts (e.g.,rat, hamster, dog, and chimpanzee) (Hsu et al., 1992, J. InfectiousDisease, 166:769), and also have the advantage of not requiringmitotically active cells for infection.

Any viral vector capable of accepting the coding sequences for the dsRNAmolecule(s) to be expressed can be used, for example vectors derivedfrom adenovirus (AV); adeno-associated virus (AAV); retroviruses (e.g,lentiviruses (LV), Rhabdoviruses, murine leukemia virus); herpes virus,and the like. The tropism of viral vectors can be modified bypseudotyping the vectors with envelope proteins or other surfaceantigens from other viruses, or by substituting different viral capsidproteins, as appropriate.

For example, lentiviral vectors featured in the invention can bepseudotyped with surface proteins from vesicular stomatitis virus (VSV),rabies, Ebola, Mokola, and the like. AAV vectors featured in theinvention can be made to target different cells by engineering thevectors to express different capsid protein serotypes. For example, anAAV vector expressing a serotype 2 capsid on a serotype 2 genome iscalled AAV 2/2. This serotype 2 capsid gene in the AAV 2/2 vector can bereplaced by a serotype 5 capsid gene to produce an AAV 2/5 vector.Techniques for constructing AAV vectors which express different capsidprotein serotypes are within the skill in the art; see, e.g., RabinowitzJ E et al. (2002), J Virol 76:791-801, the entire disclosure of which isherein incorporated by reference.

Selection of recombinant viral vectors suitable for use in theinvention, methods for inserting nucleic acid sequences for expressingthe dsRNA into the vector, and methods of delivering the viral vector tothe cells of interest are within the skill in the art. See, for example,Dornburg R (1995), Gene Therap. 2: 301-310; Eglitis M A (1988),Biotechniques 6: 608-614; Miller A D (1990), Hum Gene Therap. 1: 5-14;Anderson W F (1998), Nature 392: 25-30; and Rubinson D A et al., Nat.Genet. 33: 401-406, the entire disclosures of which are hereinincorporated by reference.

Viral vectors can be derived from AV and AAV. In one embodiment, thedsRNA featured in the invention is expressed as two separate,complementary single-stranded RNA molecules from a recombinant AAVvector having, for example, either the U6 or H1 RNA promoters, or thecytomegalovirus (CMV) promoter.

A suitable AV vector for expressing the dsRNA featured in the invention,a method for constructing the recombinant AV vector, and a method fordelivering the vector into target cells, are described in Xia H et al.(2002), Nat. Biotech. 20: 1006-1010.

Suitable AAV vectors for expressing the dsRNA featured in the invention,methods for constructing the recombinant AV vector, and methods fordelivering the vectors into target cells are described in Samulski R etal. (1987), J. Virol. 61: 3096-3101; Fisher K J et al. (1996), J. Virol,70: 520-532; Samulski R et al. (1989), J. Virol. 63: 3822-3826; U.S.Pat. Nos. 5,252,479; 5,139,941; International Patent Application No. WO94/13788; and International Patent Application No. WO 93/24641, theentire disclosures of which are herein incorporated by reference.

The promoter driving dsRNA expression in either a DNA plasmid or viralvector featured in the invention may be a eukaryotic RNA polymerase I(e.g., ribosomal RNA promoter), RNA polymerase II (e.g., CMV earlypromoter or actin promoter or U1 snRNA promoter) or generally RNApolymerase III promoter (e.g., U6 snRNA or 7SK RNA promoter) or aprokaryotic promoter, for example the T7 promoter, provided theexpression plasmid also encodes T7 RNA polymerase required fortranscription from a T7 promoter. The promoter can also direct transgeneexpression to the pancreas (see, e.g., the insulin regulatory sequencefor pancreas (Bucchini et al., 1986, Proc. Natl. Acad. Sci. USA83:2511-2515)).

In addition, expression of the transgene can be precisely regulated, forexample, by using an inducible regulatory sequence and expressionsystems such as a regulatory sequence that is sensitive to certainphysiological regulators, e.g., circulating glucose levels, or hormones(Docherty et al., 1994, FASEB J. 8:20-24). Such inducible expressionsystems, suitable for the control of transgene expression in cells or inmammals include regulation by ecdysone, by estrogen, progesterone,tetracycline, chemical inducers of dimerization, andisopropyl-beta-D1-thiogalactopyranoside (EPTG). A person skilled in theart would be able to choose the appropriate regulatory/promoter sequencebased on the intended use of the dsRNA transgene.

Generally, recombinant vectors capable of expressing dsRNA molecules aredelivered as described below, and persist in target cells.Alternatively, viral vectors can be used that provide for transientexpression of dsRNA molecules. Such vectors can be repeatedlyadministered as necessary. Once expressed, the dsRNAs bind to target RNAand modulate its function or expression. Delivery of dsRNA expressingvectors can be systemic, such as by intravenous or intramuscularadministration, by administration to target cells ex-planted from thepatient followed by reintroduction into the patient, or by any othermeans that allows for introduction into a desired target cell.

dsRNA expression DNA plasmids are typically transfected into targetcells as a complex with cationic lipid carriers (e.g., Oligofectamine)or non-cationic lipid-based carriers (e.g., Transit-TKO™). Multiplelipid transfections for dsRNA-mediated knockdowns targeting differentregions of a single XBP-1 gene or multiple XBP-1 genes over a period ofa week or more are also contemplated by the invention. Successfulintroduction of vectors into host cells can be monitored using variousknown methods. For example, transient transfection can be signaled witha reporter, such as a fluorescent marker, such as Green FluorescentProtein (GFP). Stable transfection of cells ex vivo can be ensured usingmarkers that provide the transfected cell with resistance to specificenvironmental factors (e.g., antibiotics and drugs), such as hygromycinB resistance.

The XBP-1 specific dsRNA molecules can also be inserted into vectors andused as gene therapy vectors for human patients. Gene therapy vectorscan be delivered to a subject by, for example, intravenous injection,local administration (see U.S. Pat. No. 5,328,470) or by stereotacticinjection (see e.g., Chen et al. (1994) Proc. Natl. Acad. Sci. USA91:3054-3057). The pharmaceutical preparation of the gene therapy vectorcan include the gene therapy vector in an acceptable diluent, or caninclude a slow release matrix in which the gene delivery vehicle isimbedded. Alternatively, where the complete gene delivery vector can beproduced intact from recombinant cells, e.g., retroviral vectors, thepharmaceutical preparation can include one or more cells which producethe gene delivery system.

III. Pharmaceutical Compositions Comprising dsRNA

In one embodiment, the invention provides pharmaceutical compositionscomprising a dsRNA, as described herein, and a pharmaceuticallyacceptable carrier. The pharmaceutical composition comprising the dsRNAis useful for treating a disease or disorder associated with theexpression or activity of the XBP-1 gene, such as pathological processesmediated by XBP-1 expression. Such pharmaceutical compositions areformulated based on the mode of delivery. One example is compositionsthat are formulated for systemic administration via parenteral delivery.

The pharmaceutical compositions featured herein are administered indosages sufficient to inhibit expression of the XBP-1 genes. In general,a suitable dose of total dsRNA will be in the range of 0.01 to 200.0milligrams per kilogram body weight of the recipient per day, generallyin the range of 0.02 to 50 mg per kilogram body weight per day. Forexample, the dsRNA can be administered at 0.01 mg/kg, 0.1 mg/kg, 0.05mg/kg, 0.5 mg/kg, 1 mg/kg, 2 mg/kg, 3 mg/kg, 5 mg/kg, 10 mg/kg, 20mg/kg, 30 mg/kg, 40 mg/kg, or 50 mg/kg per single dose. Thepharmaceutical composition may be administered once daily or the dsRNAmay be administered as two, three, or more sub-doses at appropriateintervals throughout the day or even using continuous infusion ordelivery through a controlled release formulation. In that case, thedsRNA contained in each sub-dose must be correspondingly smaller inorder to achieve the total daily dosage. The dosage unit can also becompounded for delivery over several days, e.g., using a conventionalsustained release formulation which provides sustained release of thedsRNA over a several day period. Sustained release formulations are wellknown in the art and are particularly useful for delivery of agents at aparticular site, such as could be used with the agents of the presentinvention. In this embodiment, the dosage unit contains a correspondingmultiple of the daily dose.

The skilled artisan will appreciate that certain factors may influencethe dosage and timing required to effectively treat a subject, includingbut not limited to the severity of the disease or disorder, previoustreatments, the general health and/or age of the subject, and otherdiseases present. Moreover, treatment of a subject with atherapeutically effective amount of a composition can include a singletreatment or a series of treatments. Estimates of effective dosages andin vivo half-lives for the individual dsRNAs encompassed by theinvention can be made using conventional methodologies or on the basisof in vivo testing using an appropriate animal model, as describedelsewhere herein.

Advances in mouse genetics have generated a number of mouse models forthe study of various human diseases, such as pathological processesmediated by XBP-1 expression. Such models are used for in vivo testingof dsRNA, as well as for determining a therapeutically effective dose.

The present invention also includes pharmaceutical compositions andformulations which include the dsRNA compounds featured in theinvention. The pharmaceutical compositions of the present invention maybe administered in a number of ways depending upon whether local orsystemic treatment is desired and upon the area to be treated.Administration may be topical (e.g., by a transdermal patch), pulmonary(e.g., by inhalation or insufflation of powders or aerosols, includingby nebulizer; intratracheal, intranasal, epidermal and transdermal),oral or parenteral. Parenteral administration includes intravenous,intraarterial, subcutaneous, intraperitoneal or intramuscular injectionor infusion; subdermal, e.g., via an implanted device; or intracranial,e.g., by intrathecal or intraventricular, administration.

Pharmaceutical compositions and formulations for topical administrationmay include transdermal patches, ointments, lotions, creams, gels,drops, suppositories, sprays, liquids and powders. Conventionalpharmaceutical carriers, aqueous, powder or oily bases, thickeners andthe like may be necessary or desirable. Coated condoms, gloves and thelike may also be useful. Suitable topical formulations include those inwhich the dsRNAs featured in the invention are in admixture with atopical delivery agent such as lipids, liposomes, fatty acids, fattyacid esters, steroids, chelating agents and surfactants. Suitable lipidsand liposomes include neutral (e.g., dioleoylphosphatidyl DOPEethanolamine, dimyristoylphosphatidyl choline DMPC,distearolyphosphatidyl choline) negative (e.g., dimyristoylphosphatidylglycerol DMPG) and cationic (e.g., dioleoyltetramethylaminopropyl DOTAPand dioleoylphosphatidyl ethanolamine DOTMA). DsRNAs featured in theinvention may be encapsulated within liposomes or may form complexesthereto, in particular to cationic liposomes. Alternatively, dsRNAs maybe complexed to lipids, in particular to cationic lipids. Suitable fattyacids and esters include but are not limited arachidonic acid, oleicacid, eicosanoic acid, lauric acid, caprylic acid, capric acid, myristicacid, palmitic acid, stearic acid, linoleic acid, linolenic acid,dicaprate, tricaprate, monoolein, dilaurin, glyceryl 1-monocaprate,1-dodecylazacycloheptan-2-one, an acylcarnitine, an acylcholine, or aC₁₋₁₀ alkyl ester (e.g., isopropylmyristate IPM), monoglyceride,diglyceride or pharmaceutically acceptable salt thereof. Topicalformulations are described in detail in U.S. patent application Ser. No.09/315,298 filed on May 20, 1999 which is incorporated herein byreference in its entirety.

In one embodiment, a dsRNA featured in the invention is fullyencapsulated in the lipid formulation (e.g., to form a SPLP, pSPLP,SNALP, or other nucleic acid-lipid particle). As used herein, the term“SNALP” refers to a stable nucleic acid-lipid particle, including SPLP.As used herein, the term “SPLP” refers to a nucleic acid-lipid particlecomprising plasmid DNA encapsulated within a lipid vesicle. SNALPs andSPLPs typically contain a cationic lipid, a non-cationic lipid, and alipid that prevents aggregation of the particle (e.g., a PEG-lipidconjugate). SNALPs and SPLPs are extremely useful for systemicapplications, as they exhibit extended circulation lifetimes followingintravenous (i.v.) injection and accumulate at distal sites (e.g., sitesphysically separated from the administration site). SPLPs include“pSPLP,” which include an encapsulated condensing agent-nucleic acidcomplex as set forth in PCT Publication No. WO 00/03683. The particlesof the present invention typically have a mean diameter of about 50 nmto about 150 nm, more typically about 60 nm to about 130 nm, moretypically about 70 nm to about 110 nm, most typically about 70 to about90 nm, and are substantially nontoxic. In addition, the nucleic acidswhen present in the nucleic acid-lipid particles of the presentinvention are resistant in aqueous solution to degradation with anuclease. Nucleic acid-lipid particles and their method of preparationare disclosed in, e.g., U.S. Pat. Nos. 5,976,567; 5,981,501; 6,534,484;6,586,410; 6,815,432; and PCT Publication No. WO 96/40964.

In one embodiment, the lipid to drug ratio (mass/mass ratio) (e.g.,lipid to dsRNA ratio) will be in the range of from about 1:1 to about50:1, from about 1:1 to about 25:1, from about 3:1 to about 15:1, fromabout 4:1 to about 10:1, from about 5:1 to about 9:1, or about 6:1 toabout 9:1.

The cationic lipid may be, for example, N,N-dioleyl-N,N-dimethylammoniumchloride (DODAC), N,N-distearyl-N,N-dimethylammonium bromide (DDAB),N-(1-(2,3-dioleoyloxy)propyl)-N,N,N-trimethylammonium chloride (DOTAP),N-(1-(2,3-dioleyloxy)propyl)-N,N,N-trimethylammonium chloride (DOTMA),N,N-dimethyl-2,3-dioleyloxy)propylamine (DODMA),1,2-DiLinoleyloxy-N,N-dimethylaminopropane (DLinDMA),1,2-Dilinolenyloxy-N,N-dimethylaminopropane (DLenDMA),1,2-Dilinoleylcarbamoyloxy-3-dimethylaminopropane (DLin-C-DAP),1,2-Dilinoleyoxy-3-(dimethylamino)acetoxypropane (DLin-DAC),1,2-Dilinoleyoxy-3-morpholinopropane (DLin-MA),1,2-Dilinoleoyl-3-dimethylaminopropane (DLinDAP),1,2-Dilinoleylthio-3-dimethylaminopropane (DLin-S-DMA),1-Linoleoyl-2-linoleyloxy-3-dimethylaminopropane (DLin-2-DMAP),1,2-Dilinoleyloxy-3-trimethylaminopropane chloride salt (DLin-TMA.Cl),1,2-Dilinoleoyl-3-trimethylaminopropane chloride salt (DLin-TAP.Cl),1,2-Dilinoleyloxy-3-(N-methylpiperazino)propane (DLin-MPZ), or3-(N,N-Dilinoleylamino)-1,2-propanediol (DLinAP),3-(N,N-Dioleylamino)-1,2-propanedio (DOAP),1,2-Dilinoleyloxo-3-(2-N,N-dimethylamino)ethoxypropane (DLin-EG-DMA),2,2-Dilinoleyl-4-dimethylaminomethyl-[1,3]-dioxolane (DLin-K-DMA), or amixture thereof. The cationic lipid may comprise from about 20 mol % toabout 50 mol % or about 40 mol % of the total lipid present in theparticle.

The non-cationic lipid may be an anionic lipid or a neutral lipidincluding, but not limited to, distearoylphosphatidylcholine (DSPC),dioleoylphosphatidylcholine (DOPC), dipalmitoylphosphatidylcholine(DPPC), dioleoylphosphatidylglycerol (DOPG),dipalmitoylphosphatidylglycerol (DPPG),dioleoyl-phosphatidylethanolamine (DOPE),palmitoyloleoylphosphatidylcholine (POPC),palmitoyloleoyl-phosphatidylethanolamine (POPE),dioleoyl-phosphatidylethanolamine4-(N-maleimidomethyl)-cyclohexane-1-carboxylate (DOPE-mal), dipalmitoylphosphatidyl ethanolamine (DPPE), dimyristoylphosphoethanolamine (DMPE),distearoyl-phosphatidyl-ethanolamine (DSPE), 16-O-monomethyl PE,16-O-dimethyl PE, 18-1-trans PE,1-stearoyl-2-oleoyl-phosphatidyethanolamine (SOPE), cholesterol, or amixture thereof. The non-cationic lipid may be from about 5 mol % toabout 90 mol %, about 10 mol %, or about 58 mol % if cholesterol isincluded, of the total lipid present in the particle.

The conjugated lipid that inhibits aggregation of particles may be, forexample, a polyethyleneglycol (PEG)-lipid including, without limitation,a PEG-diacylglycerol (DAG), a PEG-dialkyloxypropyl (DAA), aPEG-phospholipid, a PEG-ceramide (Cer), or a mixture thereof. ThePEG-DAA conjugate may be, for example, a PEG-dilauryloxypropyl (Ci₂), aPEG-dimyristyloxypropyl (Ci₄), a PEG-dipalmityloxypropyl (Ci₆), or aPEG-distearyloxypropyl (C]₈). The conjugated lipid that preventsaggregation of particles may be from 0 mol % to about 20 mol % or about2 mol % of the total lipid present in the particle.

In some embodiments, the nucleic acid-lipid particle further includescholesterol at, e.g., about 10 mol % to about 60 mol % or about 48 mol %of the total lipid present in the particle.

In one embodiment, the lipidoid ND98.4HCl (MW 1487) (Formula 1),Cholesterol (Sigma-Aldrich), and PEG-Ceramide C16 (Avanti Polar Lipids)can be used to prepare lipid-siRNA nanoparticles (i.e., LNP01particles). Stock solutions of each in ethanol can be prepared asfollows: ND98, 133 mg/mL; Cholesterol, 25 mg/mL, PEG-Ceramide C16, 100mg/mL. The ND98, Cholesterol, and PEG-Ceramide C16 stock solutions canthen be combined in a, e.g., 42:48:10 molar ratio. The combined lipidsolution can be mixed with aqueous siRNA (e.g., in sodium acetate pH 5)such that the final ethanol concentration is about 35-45% and the finalsodium acetate concentration is about 100-300 mM. Lipid-siRNAnanoparticles typically form spontaneously upon mixing. Depending on thedesired particle size distribution, the resultant nanoparticle mixturecan be extruded through a polycarbonate membrane (e.g., 100 nm cut-off)using, for example, a thermobarrel extruder, such as Lipex Extruder(Northern Lipids, Inc). In some cases, the extrusion step can beomitted. Ethanol removal and simultaneous buffer exchange can beaccomplished by, for example, dialysis or tangential flow filtration.Buffer can be exchanged with, for example, phosphate buffered saline(PBS) at about pH 7, e.g., about pH 6.9, about pH 7.0, about pH 7.1,about pH 7.2, about pH 7.3, or about pH 7.4.

LNP01 formulations are described, e.g., in International ApplicationPublication No. WO 2008/042973, which is hereby incorporated byreference.

Formulations prepared by either the standard or extrusion-free methodcan be characterized in similar manners. For example, formulations aretypically characterized by visual inspection. They should be whitishtranslucent solutions free from aggregates or sediment. Particle sizeand particle size distribution of lipid-nanoparticles can be measured bylight scattering using, for example, a Malvern Zetasizer Nano ZS(Malvern, USA). Particles should be about 20-300 nm, such as 40-100 nmin size. The particle size distribution should be unimodal. The totalsiRNA concentration in the formulation, as well as the entrappedfraction, is estimated using a dye exclusion assay. A sample of theformulated siRNA can be incubated with an RNA-binding dye, such asRibogreen (Molecular Probes) in the presence or absence of a formulationdisrupting surfactant, e.g., 0.5% Triton-X100. The total siRNA in theformulation can be determined by the signal from the sample containingthe surfactant, relative to a standard curve. The entrapped fraction isdetermined by subtracting the “free” siRNA content (as measured by thesignal in the absence of surfactant) from the total siRNA content.Percent entrapped siRNA is typically >85%. For SNALP formulation, theparticle size is at least 30 nm, at least 40 nm, at least 50 nm, atleast 60 nm, at least 70 nm, at least 80 nm, at least 90 nm, at least100 nm, at least 110 nm, and at least 120 nm. The suitable range istypically about at least 50 nm to about at least 110 nm, about at least60 nm to about at least 100 nm, or about at least 80 nm to about atleast 90 nm.

Compositions and formulations for oral administration include powders orgranules, microparticulates, nanoparticulates, suspensions or solutionsin water or non-aqueous media, capsules, gel capsules, sachets, tabletsor minitablets. Thickeners, flavoring agents, diluents, emulsifiers,dispersing aids or binders may be desirable. In some embodiments, oralformulations are those in which dsRNAs featured in the invention areadministered in conjunction with one or more penetration enhancerssurfactants and chelators. Suitable surfactants include fatty acidsand/or esters or salts thereof, bile acids and/or salts thereof.Suitable bile acids/salts include chenodeoxycholic acid (CDCA) andursodeoxychenodeoxycholic acid (UDCA), cholic acid, dehydrocholic acid,deoxycholic acid, glucholic acid, glycholic acid, glycodeoxycholic acid,taurocholic acid, taurodeoxycholic acid, sodiumtauro-24,25-dihydro-fusidate and sodium glycodihydrofusidate. Suitablefatty acids include arachidonic acid, undecanoic acid, oleic acid,lauric acid, caprylic acid, capric acid, myristic acid, palmitic acid,stearic acid, linoleic acid, linolenic acid, dicaprate, tricaprate,monoolein, dilaurin, glyceryl 1-monocaprate,1-dodecylazacycloheptan-2-one, an acylcarnitine, an acylcholine, or amonoglyceride, a diglyceride or a pharmaceutically acceptable saltthereof (e.g., sodium). In some embodiments, combinations of penetrationenhancers are used, for example, fatty acids/salts in combination withbile acids/salts. One exemplary combination is the sodium salt of lauricacid, capric acid and UDCA. Further penetration enhancers includepolyoxyethylene-9-lauryl ether, polyoxyethylene-20-cetyl ether. DsRNAsfeatured in the invention may be delivered orally, in granular formincluding sprayed dried particles, or complexed to form micro ornanoparticles. DsRNA complexing agents include poly-amino acids;polyimines; polyacrylates; polyalkylacrylates, polyoxethanes,polyalkylcyanoacrylates; cationized gelatins, albumins, starches,acrylates, polyethyleneglycols (PEG) and starches;polyalkylcyanoacrylates; DEAE-derivatized polyimines, pollulans,celluloses and starches. Suitable complexing agents include chitosan,N-trimethylchitosan, poly-L-lysine, polyhistidine, polyornithine,polyspermines, protamine, polyvinylpyridine,polythiodiethylaminomethylethylene P(TDAE), polyaminostyrene (e.g.,p-amino), poly(methylcyanoacrylate), poly(ethylcyanoacrylate),poly(butylcyanoacrylate), poly(isobutylcyanoacrylate),poly(isohexylcynaoacrylate), DEAE-methacrylate, DEAE-hexylacrylate,DEAE-acrylamide, DEAE-albumin and DEAE-dextran, polymethylacrylate,polyhexylacrylate, poly(D,L-lactic acid), poly(DL-lactic-co-glycolicacid (PLGA), alginate, and polyethyleneglycol (PEG). Oral formulationsfor dsRNAs and their preparation are described in detail in U.S.application. Ser. No. 08/886,829 (filed Jul. 1, 1997), Ser. No.09/108,673 (filed Jul. 1, 1998), Ser. No. 09/256,515 (filed Feb. 23,1999), Ser. No. 09/082,624 (filed May 21, 1998) and Ser. No. 09/315,298(filed May 20, 1999), each of which is incorporated herein by referencein their entirety.

Compositions and formulations for parenteral, intrathecal,intraventricular or intrahepatic administration may include sterileaqueous solutions which may also contain buffers, diluents and othersuitable additives such as, but not limited to, penetration enhancers,carrier compounds and other pharmaceutically acceptable carriers orexcipients.

Pharmaceutical compositions of the present invention include, but arenot limited to, solutions, emulsions, and liposome-containingformulations. These compositions may be generated from a variety ofcomponents that include, but are not limited to, preformed liquids,self-emulsifying solids and self-emulsifying semisolids. Particularlyperfered are formulations that target the liver when treating hepaticdisorders such as hepatic carcinoma.

The pharmaceutical formulations of the present invention, which mayconveniently be presented in unit dosage form, may be prepared accordingto conventional techniques well known in the pharmaceutical industry.Such techniques include the step of bringing into association the activeingredients with the pharmaceutical carrier(s) or excipient(s). Ingeneral, the formulations are prepared by uniformly and intimatelybringing into association the active ingredients with liquid carriers orfinely divided solid carriers or both, and then, if necessary, shapingthe product.

The compositions of the present invention may be formulated into any ofmany possible dosage forms such as, but not limited to, tablets,capsules, gel capsules, liquid syrups, soft gels, suppositories, andenemas. The compositions of the present invention may also be formulatedas suspensions in aqueous, non-aqueous or mixed media. Aqueoussuspensions may further contain substances which increase the viscosityof the suspension including, for example, sodium carboxymethylcellulose,sorbitol and/or dextran. The suspension may also contain stabilizers.

Emulsions

The compositions of the present invention may be prepared and formulatedas emulsions. Emulsions are typically heterogenous systems of one liquiddispersed in another in the form of droplets usually exceeding 0.1.mu.min diameter (Idson, in Pharmaceutical Dosage Forms, Lieberman, Riegerand Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1,p. 199; Rosoff, in Pharmaceutical Dosage Forms, Lieberman, Rieger andBanker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., Volume 1, p.245; Block in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker(Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 2, p. 335;Higuchi et al., in Remington's Pharmaceutical Sciences, Mack PublishingCo., Easton, Pa., 1985, p. 301). Emulsions are often biphasic systemscomprising two immiscible liquid phases intimately mixed and dispersedwith each other. In general, emulsions may be of either the water-in-oil(w/o) or the oil-in-water (o/w) variety. When an aqueous phase is finelydivided into and dispersed as minute droplets into a bulk oily phase,the resulting composition is called a water-in-oil (w/o) emulsion.Alternatively, when an oily phase is finely divided into and dispersedas minute droplets into a bulk aqueous phase, the resulting compositionis called an oil-in-water (o/w) emulsion. Emulsions may containadditional components in addition to the dispersed phases, and theactive drug which may be present as a solution in either the aqueousphase, oily phase or itself as a separate phase. Pharmaceuticalexcipients such as emulsifiers, stabilizers, dyes, and anti-oxidants mayalso be present in emulsions as needed. Pharmaceutical emulsions mayalso be multiple emulsions that are comprised of more than two phasessuch as, for example, in the case of oil-in-water-in-oil (o/w/o) andwater-in-oil-in-water (w/o/w) emulsions. Such complex formulations oftenprovide certain advantages that simple binary emulsions do not. Multipleemulsions in which individual oil droplets of an o/w emulsion enclosesmall water droplets constitute a w/o/w emulsion. Likewise a system ofoil droplets enclosed in globules of water stabilized in an oilycontinuous phase provides an o/w/o emulsion.

Emulsions are characterized by little or no thermodynamic stability.Often, the dispersed or discontinuous phase of the emulsion is welldispersed into the external or continuous phase and maintained in thisform through the means of emulsifiers or the viscosity of theformulation. Either of the phases of the emulsion may be a semisolid ora solid, as is the case of emulsion-style ointment bases and creams.Other means of stabilizing emulsions entail the use of emulsifiers thatmay be incorporated into either phase of the emulsion. Emulsifiers maybroadly be classified into four categories: synthetic surfactants,naturally occurring emulsifiers, absorption bases, and finely dispersedsolids (Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger andBanker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p.199).

Synthetic surfactants, also known as surface active agents, have foundwide applicability in the formulation of emulsions and have beenreviewed in the literature (Rieger, in Pharmaceutical Dosage Forms,Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., NewYork, N.Y., volume 1, p. 285; Idson, in Pharmaceutical Dosage Forms,Lieberman, Rieger and Banker (Eds.), Marcel Dekker, Inc., New York,N.Y., 1988, volume 1, p. 199). Surfactants are typically amphiphilic andcomprise a hydrophilic and a hydrophobic portion. The ratio of thehydrophilic to the hydrophobic nature of the surfactant has been termedthe hydrophile/lipophile balance (HLB) and is a valuable tool incategorizing and selecting surfactants in the preparation offormulations. Surfactants may be classified into different classes basedon the nature of the hydrophilic group: nonionic, anionic, cationic andamphoteric (Rieger, in Pharmaceutical Dosage Forms, Lieberman, Riegerand Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1,p. 285).

Naturally occurring emulsifiers used in emulsion formulations includelanolin, beeswax, phosphatides, lecithin and acacia. Absorption basespossess hydrophilic properties such that they can soak up water to formw/o emulsions yet retain their semisolid consistencies, such asanhydrous lanolin and hydrophilic petrolatum. Finely divided solids havealso been used as good emulsifiers especially in combination withsurfactants and in viscous preparations. These include polar inorganicsolids, such as heavy metal hydroxides, nonswelling clays such asbentonite, attapulgite, hectorite, kaolin, montmorillonite, colloidalaluminum silicate and colloidal magnesium aluminum silicate, pigmentsand nonpolar solids such as carbon or glyceryl tristearate.

A large variety of non-emulsifying materials are also included inemulsion formulations and contribute to the properties of emulsions.These include fats, oils, waxes, fatty acids, fatty alcohols, fattyesters, humectants, hydrophilic colloids, preservatives and antioxidants(Block, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker(Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 335;Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker(Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 199).

Hydrophilic colloids or hydrocolloids include naturally occurring gumsand synthetic polymers such as polysaccharides (for example, acacia,agar, alginic acid, carrageenan, guar gum, karaya gum, and tragacanth),cellulose derivatives (for example, carboxymethylcellulose andcarboxypropylcellulose), and synthetic polymers (for example, carbomers,cellulose ethers, and carboxyvinyl polymers). These disperse or swell inwater to form colloidal solutions that stabilize emulsions by formingstrong interfacial films around the dispersed-phase droplets and byincreasing the viscosity of the external phase.

Since emulsions often contain a number of ingredients such ascarbohydrates, proteins, sterols and phosphatides that may readilysupport the growth of microbes, these formulations often incorporatepreservatives. Commonly used preservatives included in emulsionformulations include methyl paraben, propyl paraben, quaternary ammoniumsalts, benzalkonium chloride, esters of p-hydroxybenzoic acid, and boricacid. Antioxidants are also commonly added to emulsion formulations toprevent deterioration of the formulation. Antioxidants used may be freeradical scavengers such as tocopherols, alkyl gallates, butylatedhydroxyanisole, butylated hydroxytoluene, or reducing agents such asascorbic acid and sodium metabisulfite, and antioxidant synergists suchas citric acid, tartaric acid, and lecithin.

The application of emulsion formulations via dermatological, oral andparenteral routes and methods for their manufacture have been reviewedin the literature (Idson, in Pharmaceutical Dosage Forms, Lieberman,Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y.,volume 1, p. 199). Emulsion formulations for oral delivery have beenvery widely used because of ease of formulation, as well as efficacyfrom an absorption and bioavailability standpoint (Rosoff, inPharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988,Marcel Dekker, Inc., New York, N.Y., volume 1, p. 245; Idson, inPharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988,Marcel Dekker, Inc., New York, N.Y., volume 1, p. 199). Mineral-oil baselaxatives, oil-soluble vitamins and high fat nutritive preparations areamong the materials that have commonly been administered orally as o/wemulsions.

In one embodiment of the present invention, the compositions of dsRNAsand nucleic acids are formulated as microemulsions. A microemulsion maybe defined as a system of water, oil and amphiphile which is a singleoptically isotropic and thermodynamically stable liquid solution(Rosoff, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker(Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 245).Typically microemulsions are systems that are prepared by firstdispersing an oil in an aqueous surfactant solution and then adding asufficient amount of a fourth component, generally an intermediatechain-length alcohol to form a transparent system. Therefore,microemulsions have also been described as thermodynamically stable,isotropically clear dispersions of two immiscible liquids that arestabilized by interfacial films of surface-active molecules (Leung andShah, in: Controlled Release of Drugs: Polymers and Aggregate Systems,Rosoff, M., Ed., 1989, VCH Publishers, New York, pages 185-215).Microemulsions commonly are prepared via a combination of three to fivecomponents that include oil, water, surfactant, cosurfactant andelectrolyte. Whether the microemulsion is of the water-in-oil (w/o) oran oil-in-water (o/w) type is dependent on the properties of the oil andsurfactant used and on the structure and geometric packing of the polarheads and hydrocarbon tails of the surfactant molecules (Schott, inRemington's Pharmaceutical Sciences, Mack Publishing Co., Easton, Pa.,1985, p. 271).

The phenomenological approach utilizing phase diagrams has beenextensively studied and has yielded a comprehensive knowledge, to oneskilled in the art, of how to formulate microemulsions (Rosoff, inPharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988,Marcel Dekker, Inc., New York, N.Y., volume 1, p. 245; Block, inPharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988,Marcel Dekker, Inc., New York, N.Y., volume 1, p. 335). Compared toconventional emulsions, microemulsions offer the advantage ofsolubilizing water-insoluble drugs in a formulation of thermodynamicallystable droplets that are formed spontaneously.

Surfactants used in the preparation of microemulsions include, but arenot limited to, ionic surfactants, non-ionic surfactants, Brij 96,polyoxyethylene oleyl ethers, polyglycerol fatty acid esters,tetraglycerol monolaurate (ML310), tetraglycerol monooleate (MO310),hexaglycerol monooleate (PO310), hexaglycerol pentaoleate (PO500),decaglycerol monocaprate (MCA750), decaglycerol monooleate (MO750),decaglycerol sequioleate (SO750), decaglycerol decaoleate (DAO750),alone or in combination with cosurfactants. The cosurfactant, usually ashort-chain alcohol such as ethanol, 1-propanol, and 1-butanol, servesto increase the interfacial fluidity by penetrating into the surfactantfilm and consequently creating a disordered film because of the voidspace generated among surfactant molecules. Microemulsions may, however,be prepared without the use of cosurfactants and alcohol-freeself-emulsifying microemulsion systems are known in the art. The aqueousphase may typically be, but is not limited to, water, an aqueoussolution of the drug, glycerol, PEG300, PEG400, polyglycerols, propyleneglycols, and derivatives of ethylene glycol. The oil phase may include,but is not limited to, materials such as Captex 300, Captex 355, CapmulMCM, fatty acid esters, medium chain (C8-C12) mono, di, andtri-glycerides, polyoxyethylated glyceryl fatty acid esters, fattyalcohols, polyglycolized glycerides, saturated polyglycolized C8-C10glycerides, vegetable oils and silicone oil.

Microemulsions are particularly of interest from the standpoint of drugsolubilization and the enhanced absorption of drugs. Lipid basedmicroemulsions (both o/w and w/o) have been proposed to enhance the oralbioavailability of drugs, including peptides (Constantinides et al.,Pharmaceutical Research, 1994, 11, 1385-1390; Ritschel, Meth. Find. Exp.Clin. Pharmacol., 1993, 13, 205). Microemulsions afford advantages ofimproved drug solubilization, protection of drug from enzymatichydrolysis, possible enhancement of drug absorption due tosurfactant-induced alterations in membrane fluidity and permeability,ease of preparation, ease of oral administration over solid dosageforms, improved clinical potency, and decreased toxicity (Constantinideset al., Pharmaceutical Research, 1994, 11, 1385; Ho et al., J. Pharm.Sci., 1996, 85, 138-143). Often microemulsions may form spontaneouslywhen their components are brought together at ambient temperature. Thismay be particularly advantageous when formulating thermolabile drugs,peptides or dsRNAs. Microemulsions have also been effective in thetransdermal delivery of active components in both cosmetic andpharmaceutical applications. It is expected that the microemulsioncompositions and formulations of the present invention will facilitatethe increased systemic absorption of dsRNAs and nucleic acids from thegastrointestinal tract, as well as improve the local cellular uptake ofdsRNAs and nucleic acids.

Microemulsions of the present invention may also contain additionalcomponents and additives such as sorbitan monostearate (Grill 3),Labrasol, and penetration enhancers to improve the properties of theformulation and to enhance the absorption of the dsRNAs and nucleicacids of the present invention. Penetration enhancers used in themicroemulsions of the present invention may be classified as belongingto one of five broad categories—surfactants, fatty acids, bile salts,chelating agents, and non-chelating non-surfactants (Lee et al.,Critical Reviews in Therapeutic Drug Carrier Systems, 1991, p. 92). Eachof these classes has been discussed above.

Liposomes

There are many organized surfactant structures besides microemulsionsthat have been studied and used for the formulation of drugs. Theseinclude monolayers, micelles, bilayers and vesicles. Vesicles, such asliposomes, have attracted great interest because of their specificityand the duration of action they offer from the standpoint of drugdelivery. As used in the present invention, the term “liposome” means avesicle composed of amphiphilic lipids arranged in a spherical bilayeror bilayers.

Liposomes are unilamellar or multilamellar vesicles which have amembrane formed from a lipophilic material and an aqueous interior. Theaqueous portion contains the composition to be delivered. Cationicliposomes possess the advantage of being able to fuse to the cell wall.Non-cationic liposomes, although not able to fuse as efficiently withthe cell wall, are taken up by macrophages in vivo.

In order to cross intact mammalian skin, lipid vesicles must passthrough a series of fine pores, each with a diameter less than 50 nm,under the influence of a suitable transdermal gradient. Therefore, it isdesirable to use a liposome which is highly deformable and able to passthrough such fine pores.

Further advantages of liposomes include; liposomes obtained from naturalphospholipids are biocompatible and biodegradable; liposomes canincorporate a wide range of water and lipid soluble drugs; liposomes canprotect encapsulated drugs in their internal compartments frommetabolism and degradation (Rosoff, in Pharmaceutical Dosage Forms,Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., NewYork, N.Y., volume 1, p. 245). Important considerations in thepreparation of liposome formulations are the lipid surface charge,vesicle size and the aqueous volume of the liposomes.

Liposomes are useful for the transfer and delivery of active ingredientsto the site of action. Because the liposomal membrane is structurallysimilar to biological membranes, when liposomes are applied to a tissue,the liposomes start to merge with the cellular membranes and as themerging of the liposome and cell progresses, the liposomal contents areemptied into the cell where the active agent may act.

Liposomal formulations have been the focus of extensive investigation asthe mode of delivery for many drugs. There is growing evidence that fortopical administration, liposomes present several advantages over otherformulations. Such advantages include reduced side-effects related tohigh systemic absorption of the administered drug, increasedaccumulation of the administered drug at the desired target, and theability to administer a wide variety of drugs, both hydrophilic andhydrophobic, into the skin.

Several reports have detailed the ability of liposomes to deliver agentsincluding high-molecular weight DNA into the skin. Compounds includinganalgesics, antibodies, hormones and high-molecular weight DNAs havebeen administered to the skin. The majority of applications resulted inthe targeting of the upper epidermis

Liposomes fall into two broad classes. Cationic liposomes are positivelycharged liposomes which interact with the negatively charged DNAmolecules to form a stable complex. The positively charged DNA/liposomecomplex binds to the negatively charged cell surface and is internalizedin an endosome. Due to the acidic pH within the endosome, the liposomesare ruptured, releasing their contents into the cell cytoplasm (Wang etal., Biochem. Biophys. Res. Commun., 1987, 147, 980-985).

Liposomes which are pH-sensitive or negatively-charged, entrap DNArather than complex with it. Since both the DNA and the lipid aresimilarly charged, repulsion rather than complex formation occurs.Nevertheless, some DNA is entrapped within the aqueous interior of theseliposomes. pH-sensitive liposomes have been used to deliver DNA encodingthe thymidine kinase gene to cell monolayers in culture. Expression ofthe exogenous gene was detected in the target cells (Zhou et al.,Journal of Controlled Release, 1992, 19, 269-274).

One major type of liposomal composition includes phospholipids otherthan naturally-derived phosphatidylcholine. Neutral liposomecompositions, for example, can be formed from dimyristoylphosphatidylcholine (DMPC) or dipalmitoyl phosphatidylcholine (DPPC).Anionic liposome compositions generally are formed from dimyristoylphosphatidylglycerol, while anionic fusogenic liposomes are formedprimarily from dioleoyl phosphatidylethanolamine (DOPE). Another type ofliposomal composition is formed from phosphatidylcholine (PC) such as,for example, soybean PC, and egg PC. Another type is formed frommixtures of phospholipid and/or phosphatidylcholine and/or cholesterol.

Several studies have assessed the topical delivery of liposomal drugformulations to the skin. Application of liposomes containing interferonto guinea pig skin resulted in a reduction of skin herpes sores whiledelivery of interferon via other means (e.g., as a solution or as anemulsion) were ineffective (Weiner et al., Journal of Drug Targeting,1992, 2, 405-410). Further, an additional study tested the efficacy ofinterferon administered as part of a liposomal formulation to theadministration of interferon using an aqueous system, and concluded thatthe liposomal formulation was superior to aqueous administration (duPlessis et al., Antiviral Research, 1992, 18, 259-265).

Non-ionic liposomal systems have also been examined to determine theirutility in the delivery of drugs to the skin, in particular systemscomprising non-ionic surfactant and cholesterol. Non-ionic liposomalformulations comprising Novasome™ I (glyceryldilaurate/cholesterol/po-lyoxyethylene-10-stearyl ether) and Novasome™II (glyceryl distearate/cholesterol/polyoxyethylene-10-stearyl ether)were used to deliver cyclosporin-A into the dermis of mouse skin.Results indicated that such non-ionic liposomal systems were effectivein facilitating the deposition of cyclosporin-A into different layers ofthe skin (Hu et al. S.T.P.Pharma. Sci., 1994, 4, 6, 466).

Liposomes also include “sterically stabilized” liposomes, a term which,as used herein, refers to liposomes comprising one or more specializedlipids that, when incorporated into liposomes, result in enhancedcirculation lifetimes relative to liposomes lacking such specializedlipids. Examples of sterically stabilized liposomes are those in whichpart of the vesicle-forming lipid portion of the liposome (A) comprisesone or more glycolipids, such as monosialoganglioside GM₁, or (B) isderivatized with one or more hydrophilic polymers, such as apolyethylene glycol (PEG) moiety. While not wishing to be bound by anyparticular theory, it is thought in the art that, at least forsterically stabilized liposomes containing gangliosides, sphingomyelin,or PEG-derivatized lipids, the enhanced circulation half-life of thesesterically stabilized liposomes derives from a reduced uptake into cellsof the reticuloendothelial system (RES) (Allen et al., FEBS Letters,1987, 223, 42; Wu et al., Cancer Research, 1993, 53, 3765).

Various liposomes comprising one or more glycolipids are known in theart. Papahadjopoulos et al. (Ann. N.Y. Acad. Sci., 1987, 507, 64)reported the ability of monosialoganglioside GM₁, galactocerebrosidesulfate and phosphatidylinositol to improve blood half-lives ofliposomes. These findings were expounded upon by Gabizon et al. (Proc.Natl. Acad. Sci. U.S.A., 1988, 85, 6949). U.S. Pat. No. 4,837,028 and WO88/04924, both to Allen et al., disclose liposomes comprising (1)sphingomyelin and (2) the ganglioside GM₁ or a galactocerebrosidesulfate ester. U.S. Pat. No. 5,543,152 (Webb et al.) discloses liposomescomprising sphingomyelin. Liposomes comprising1,2-sn-dimyristoylphosphat-idylcholine are disclosed in WO 97/13499 (Limet al).

Many liposomes comprising lipids derivatized with one or morehydrophilic polymers, and methods of preparation thereof, are known inthe art. Sunamoto et al. (Bull. Chem. Soc. Jpn., 1980, 53, 2778)described liposomes comprising a nonionic detergent, 2C₁₂15G, thatcontains a PEG moiety. Illum et al. (FEBS Lett., 1984, 167, 79) notedthat hydrophilic coating of polystyrene particles with polymeric glycolsresults in significantly enhanced blood half-lives. Syntheticphospholipids modified by the attachment of carboxylic groups ofpolyalkylene glycols (e.g., PEG) are described by Sears (U.S. Pat. Nos.4,426,330 and 4,534,899). Klibanov et al. (FEBS Lett., 1990, 268, 235)described experiments demonstrating that liposomes comprisingphosphatidylethanolamine (PE) derivatized with PEG or PEG stearate havesignificant increases in blood circulation half-lives. Blume et al.(Biochimica et Biophysica Acta, 1990, 1029, 91) extended suchobservations to other PEG-derivatized phospholipids, e.g., DSPE-PEG,formed from the combination of distearoylphosphatidylethanolamine (DSPE)and PEG. Liposomes having covalently bound PEG moieties on theirexternal surface are described in European Patent No. EP 0 445 131 B1and WO 90/04384 to Fisher. Liposome compositions containing 1-20 molepercent of PE derivatized with PEG, and methods of use thereof, aredescribed by Woodle et al. (U.S. Pat. Nos. 5,013,556 and 5,356,633) andMartin et al. (U.S. Pat. No. 5,213,804 and European Patent No. EP 0 496813 B1). Liposomes comprising a number of other lipid-polymer conjugatesare disclosed in WO 91/05545 and U.S. Pat. No. 5,225,212 (both to Martinet al.) and in WO 94/20073 (Zalipsky et al.) Liposomes comprisingPEG-modified ceramide lipids are described in WO 96/10391 (Choi et al).U.S. Pat. No. 5,540,935 (Miyazaki et al.) and U.S. Pat. No. 5,556,948(Tagawa et al.) describe PEG-containing liposomes that can be furtherderivatized with functional moieties on their surfaces.

A limited number of liposomes comprising nucleic acids are known in theart. WO 96/40062 to Thierry et al. discloses methods for encapsulatinghigh molecular weight nucleic acids in liposomes. U.S. Pat. No.5,264,221 to Tagawa et al. discloses protein-bonded liposomes andasserts that the contents of such liposomes may include an dsRNA RNA.U.S. Pat. No. 5,665,710 to Rahman et al. describes certain methods ofencapsulating oligodeoxynucleotides in liposomes. WO 97/04787 to Love etal. discloses liposomes comprising dsRNA dsRNAs targeted to the rafgene.

Transfersomes are yet another type of liposomes, and are highlydeformable lipid aggregates which are attractive candidates for drugdelivery vehicles. Transfersomes may be described as lipid dropletswhich are so highly deformable that they are easily able to penetratethrough pores which are smaller than the droplet. Transfersomes areadaptable to the environment in which they are used, e.g., they areself-optimizing (adaptive to the shape of pores in the skin),self-repairing, frequently reach their targets without fragmenting, andoften self-loading. To make transfersomes it is possible to add surfaceedge-activators, usually surfactants, to a standard liposomalcomposition. Transfersomes have been used to deliver serum albumin tothe skin. The transfersome-mediated delivery of serum albumin has beenshown to be as effective as subcutaneous injection of a solutioncontaining serum albumin.

Surfactants find wide application in formulations such as emulsions(including microemulsions) and liposomes. The most common way ofclassifying and ranking the properties of the many different types ofsurfactants, both natural and synthetic, is by the use of thehydrophile/lipophile balance (HLB). The nature of the hydrophilic group(also known as the “head”) provides the most useful means forcategorizing the different surfactants used in formulations (Rieger, inPharmaceutical Dosage Forms, Marcel Dekker, Inc., New York, N.Y., 1988,p. 285).

If the surfactant molecule is not ionized, it is classified as anonionic surfactant. Nonionic surfactants find wide application inpharmaceutical and cosmetic products and are usable over a wide range ofpH values. In general their HLB values range from 2 to about 18depending on their structure. Nonionic surfactants include nonionicesters such as ethylene glycol esters, propylene glycol esters, glycerylesters, polyglyceryl esters, sorbitan esters, sucrose esters, andethoxylated esters. Nonionic alkanolamides and ethers such as fattyalcohol ethoxylates, propoxylated alcohols, and ethoxylated/propoxylatedblock polymers are also included in this class. The polyoxyethylenesurfactants are the most popular members of the nonionic surfactantclass.

If the surfactant molecule carries a negative charge when it isdissolved or dispersed in water, the surfactant is classified asanionic. Anionic surfactants include carboxylates such as soaps, acyllactylates, acyl amides of amino acids, esters of sulfuric acid such asalkyl sulfates and ethoxylated alkyl sulfates, sulfonates such as alkylbenzene sulfonates, acyl isethionates, acyl taurates andsulfosuccinates, and phosphates. The most important members of theanionic surfactant class are the alkyl sulfates and the soaps.

If the surfactant molecule carries a positive charge when it isdissolved or dispersed in water, the surfactant is classified ascationic. Cationic surfactants include quaternary ammonium salts andethoxylated amines. The quaternary ammonium salts are the most usedmembers of this class.

If the surfactant molecule has the ability to carry either a positive ornegative charge, the surfactant is classified as amphoteric. Amphotericsurfactants include acrylic acid derivatives, substituted alkylamides,N-alkylbetaines and phosphatides.

The use of surfactants in drug products, formulations and in emulsionshas been reviewed (Rieger, in Pharmaceutical Dosage Forms, MarcelDekker, Inc., New York, N.Y., 1988, p. 285).

Penetration Enhancers

In one embodiment, the present invention employs various penetrationenhancers to effect the efficient delivery of nucleic acids,particularly dsRNAs, to the skin of animals. Most drugs are present insolution in both ionized and nonionized forms. However, usually onlylipid soluble or lipophilic drugs readily cross cell membranes. It hasbeen discovered that even non-lipophilic drugs may cross cell membranesif the membrane to be crossed is treated with a penetration enhancer. Inaddition to aiding the diffusion of non-lipophilic drugs across cellmembranes, penetration enhancers also enhance the permeability oflipophilic drugs.

Penetration enhancers may be classified as belonging to one of fivebroad categories, i.e., surfactants, fatty acids, bile salts, chelatingagents, and non-chelating non-surfactants (Lee et al., Critical Reviewsin Therapeutic Drug Carrier Systems, 1991, p. 92). Each of the abovementioned classes of penetration enhancers are described below ingreater detail.

Surfactants: In connection with the present invention, surfactants (or“surface-active agents”) are chemical entities which, when dissolved inan aqueous solution, reduce the surface tension of the solution or theinterfacial tension between the aqueous solution and another liquid,with the result that absorption of dsRNAs through the mucosa isenhanced. In addition to bile salts and fatty acids, these penetrationenhancers include, for example, sodium lauryl sulfate,polyoxyethylene-9-lauryl ether and polyoxyethylene-20-cetyl ether) (Leeet al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, p.92); and perfluorochemical emulsions, such as FC-43. Takahashi et al.,J. Pharm. Pharmacol., 1988, 40, 252).

Fatty acids: Various fatty acids and their derivatives which act aspenetration enhancers include, for example, oleic acid, lauric acid,capric acid (n-decanoic acid), myristic acid, palmitic acid, stearicacid, linoleic acid, linolenic acid, dicaprate, tricaprate, monoolein(1-monooleoyl-rac-glycerol), dilaurin, caprylic acid, arachidonic acid,glycerol 1-monocaprate, 1-dodecylazacycloheptan-2-one, acylcarnitines,acylcholines, C₁₋₁₀ alkyl esters thereof (e.g., methyl, isopropyl andt-butyl), and mono- and di-glycerides thereof (i.e., oleate, laurate,caprate, myristate, palmitate, stearate, linoleate, etc.) (Lee et al.,Critical Reviews in Therapeutic Drug Carryier Systems, 1991, p. 92;Muranishi, Critical Reviews in Therapeutic Drug Carrier Systems, 1990,7, 1-33; El Hariri et al., J. Pharm. Pharmacol., 1992, 44, 651-654).

Bile salts: The physiological role of bile includes the facilitation ofdispersion and absorption of lipids and fat-soluble vitamins (Brunton,Chapter 38 in: Goodman & Gilman's The Pharmacological Basis ofTherapeutics, 9th Ed., Hardman et al. Eds., McGraw-Hill, New York, 1996,pp. 934-935). Various natural bile salts, and their syntheticderivatives, act as penetration enhancers. Thus the term “bile salts”includes any of the naturally occurring components of bile as well asany of their synthetic derivatives. Suitable bile salts include, forexample, cholic acid (or its pharmaceutically acceptable sodium salt,sodium cholate), dehydrocholic acid (sodium dehydrocholate), deoxycholicacid (sodium deoxycholate), glucholic acid (sodium glucholate),glycholic acid (sodium glycocholate), glycodeoxycholic acid (sodiumglycodeoxycholate), taurocholic acid (sodium taurocholate),taurodeoxycholic acid (sodium taurodeoxycholate), chenodeoxycholic acid(sodium chenodeoxycholate), ursodeoxycholic acid (UDCA), sodiumtauro-24,25-dihydro-fusidate (STDHF), sodium glycodihydrofusidate andpolyoxyethylene-9-lauryl ether (POE) (Lee et al., Critical Reviews inTherapeutic Drug Carrier Systems, 1991, page 92; Swinyard, Chapter 39In: Remington's Pharmaceutical Sciences, 18th Ed., Gennaro, ed., MackPublishing Co., Easton, Pa., 1990, pages 782-783; Muranishi, CriticalReviews in Therapeutic Drug Carrier Systems, 1990, 7, 1-33; Yamamoto etal., J. Pharm. Exp. Ther., 1992, 263, 25; Yamashita et al., J. Pharm.Sci., 1990, 79, 579-583).

Chelating Agents: Chelating agents, as used in connection with thepresent invention, can be defined as compounds that remove metallic ionsfrom solution by forming complexes therewith, with the result thatabsorption of dsRNAs through the mucosa is enhanced. With regards totheir use as penetration enhancers in the present invention, chelatingagents have the added advantage of also serving as DNase inhibitors, asmost characterized DNA nucleases require a divalent metal ion forcatalysis and are thus inhibited by chelating agents (Jarrett, J.Chromatogr., 1993, 618, 315-339). Suitable chelating agents include butare not limited to disodium ethylenediaminetetraacetate (EDTA), citricacid, salicylates (e.g., sodium salicylate, 5-methoxysalicylate andhomovanilate), N-acyl derivatives of collagen, laureth-9 and N-aminoacyl derivatives of beta-diketones (enamines)(Lee et al., CriticalReviews in Therapeutic Drug Carrier Systems, 1991, page 92; Muranishi,Critical Reviews in Therapeutic Drug Carrier Systems, 1990, 7, 1-33;Buur et al., J. Control Rel., 1990, 14, 43-51).

Non-chelating non-surfactants: As used herein, non-chelatingnon-surfactant penetration enhancing compounds can be defined ascompounds that demonstrate insignificant activity as chelating agents oras surfactants but that nonetheless enhance absorption of dsRNAs throughthe alimentary mucosa (Muranishi, Critical Reviews in Therapeutic DrugCarrier Systems, 1990, 7, 1-33). This class of penetration enhancersinclude, for example, unsaturated cyclic ureas, 1-alkyl- and1-alkenylazacyclo-alkanone derivatives (Lee et al., Critical Reviews inTherapeutic Drug Carrier Systems, 1991, page 92); and non-steroidalanti-inflammatory agents such as diclofenac sodium, indomethacin andphenylbutazone (Yamashita et al., J. Pharm. Pharmacol., 1987, 39,621-626).

Agents that enhance uptake of dsRNAs at the cellular level may also beadded to the pharmaceutical and other compositions of the presentinvention. For example, cationic lipids, such as lipofectin (Junichi etal, U.S. Pat. No. 5,705,188), cationic glycerol derivatives, andpolycationic molecules, such as polylysine (Lollo et al., PCTApplication WO 97/30731), are also known to enhance the cellular uptakeof dsRNAs.

Other agents may be utilized to enhance the penetration of theadministered nucleic acids, including glycols such as ethylene glycoland propylene glycol, pyrrols such as 2-pyrrol, azones, and terpenessuch as limonene and menthone.

Carriers

Certain compositions of the present invention also incorporate carriercompounds in the formulation. As used herein, “carrier compound” or“carrier” can refer to a nucleic acid, or analog thereof, which is inert(i.e., does not possess biological activity per se) but is recognized asa nucleic acid by in vivo processes that reduce the bioavailability of anucleic acid having biological activity by, for example, degrading thebiologically active nucleic acid or promoting its removal fromcirculation. The coadministration of a nucleic acid and a carriercompound, typically with an excess of the latter substance, can resultin a substantial reduction of the amount of nucleic acid recovered inthe liver, kidney or other extracirculatory reservoirs, presumably dueto competition between the carrier compound and the nucleic acid for acommon receptor. For example, the recovery of a partiallyphosphorothioate dsRNA in hepatic tissue can be reduced when it iscoadministered with polyinosinic acid, dextran sulfate, polycytidic acidor 4-acetamido-4′ isothiocyano-stilbene-2,2′-disulfonic acid (Miyao etal., DsRNA Res. Dev., 1995, 5, 115-121; Takakura et al., DsRNA & Nucl.Acid Drug Dev., 1996, 6, 177-183.

Excipients

In contrast to a carrier compound, a “pharmaceutical carrier” or“excipient” is a pharmaceutically acceptable solvent, suspending agentor any other pharmacologically inert vehicle for delivering one or morenucleic acids to an animal. The excipient may be liquid or solid and isselected, with the planned manner of administration in mind, so as toprovide for the desired bulk, consistency, etc., when combined with anucleic acid and the other components of a given pharmaceuticalcomposition. Typical pharmaceutical carriers include, but are notlimited to, binding agents (e.g., pregelatinized maize starch,polyvinylpyrrolidone or hydroxypropyl methylcellulose, etc.); fillers(e.g., lactose and other sugars, microcrystalline cellulose, pectin,gelatin, calcium sulfate, ethyl cellulose, polyacrylates or calciumhydrogen phosphate, etc.); lubricants (e.g., magnesium stearate, talc,silica, colloidal silicon dioxide, stearic acid, metallic stearates,hydrogenated vegetable oils, corn starch, polyethylene glycols, sodiumbenzoate, sodium acetate, etc.); disintegrants (e.g., starch, sodiumstarch glycolate, etc.); and wetting agents (e.g., sodium laurylsulphate, etc).

Pharmaceutically acceptable organic or inorganic excipient suitable fornon-parenteral administration which do not deleteriously react withnucleic acids can also be used to formulate the compositions of thepresent invention. Suitable pharmaceutically acceptable carriersinclude, but are not limited to, water, salt solutions, alcohols,polyethylene glycols, gelatin, lactose, amylose, magnesium stearate,talc, silicic acid, viscous paraffin, hydroxymethylcellulose,polyvinylpyrrolidone and the like.

Formulations for topical administration of nucleic acids may includesterile and non-sterile aqueous solutions, non-aqueous solutions incommon solvents such as alcohols, or solutions of the nucleic acids inliquid or solid oil bases. The solutions may also contain buffers,diluents and other suitable additives. Pharmaceutically acceptableorganic or inorganic excipients suitable for non-parenteraladministration which do not deleteriously react with nucleic acids canbe used.

Suitable pharmaceutically acceptable excipients include, but are notlimited to, water, salt solutions, alcohol, polyethylene glycols,gelatin, lactose, amylose, magnesium stearate, talc, silicic acid,viscous paraffin, hydroxymethylcellulose, polyvinylpyrrolidone and thelike.

Other Components

The compositions of the present invention may additionally contain otheradjunct components conventionally found in pharmaceutical compositions,at their art-established usage levels. Thus, for example, thecompositions may contain additional, compatible, pharmaceutically-activematerials such as, for example, antipruritics, astringents, localanesthetics or anti-inflammatory agents, or may contain additionalmaterials useful in physically formulating various dosage forms of thecompositions of the present invention, such as dyes, flavoring agents,preservatives, antioxidants, opacifiers, thickening agents andstabilizers. However, such materials, when added, should not undulyinterfere with the biological activities of the components of thecompositions of the present invention. The formulations can besterilized and, if desired, mixed with auxiliary agents, e.g.,lubricants, preservatives, stabilizers, wetting agents, emulsifiers,salts for influencing osmotic pressure, buffers, colorings, flavoringsand/or aromatic substances and the like which do not deleteriouslyinteract with the nucleic acid(s) of the formulation.

Aqueous suspensions may contain substances which increase the viscosityof the suspension including, for example, sodium carboxymethylcellulose,sorbitol and/or dextran. The suspension may also contain stabilizers.

In some embodiments, pharmaceutical compositions featured in theinvention include (a) one or more dsRNA compounds and (b) one or moreother chemotherapeutic agents which function by a non-RNAi mechanism.Examples of such chemotherapeutic agents include but are not limited todaunorubicin, daunomycin, dactinomycin, doxorubicin, epirubicin,idarubicin, esorubicin, bleomycin, mafosfamide, ifosfamide, cytosinearabinoside, bis-chloroethylnitrosurea, busulfan, mitomycin C,actinomycin D, mithramycin, prednisone, hydroxyprogesterone,testosterone, tamoxifen, dacarbazine, procarbazine, hexamethylmelamine,pentamethylmelamine, mitoxantrone, amsacrine, chlorambucil,methylcyclohexylnitrosurea, nitrogen mustards, melphalan,cyclophosphamide, 6-mercaptopurine, 6-thioguanine, cytarabine,5-azacytidine, hydroxyurea, deoxycoformycin,4-hydroxyperoxycyclophosphor-amide, 5-fluorouracil (5-FU),5-fluorodeoxyuridine (5-FUdR), methotrexate (MTX), colchicine, taxol,vincristine, vinblastine, etoposide (VP-16), trimeterxate, irinotecan,topotecan, gemcitabine, teniposide, cisplatin and diethylstilbestrol(DES). See, generally, The Merck Manual of Diagnosis and Therapy, 15thEd. 1987, pp. 1206-1228, Berkow et al., eds., Rahway, N.J. When usedwith the dsRNAs featured in the invention, such chemotherapeutic agentsmay be used individually (e.g., 5-FU and oligonucleotide), sequentially(e.g., 5-FU and oligonucleotide for a period of time followed by MTX andoligonucleotide), or in combination with one or more other suchchemotherapeutic agents (e.g., 5-FU, MTX and oligonucleotide, or 5-FU,radiotherapy and oligonucleotide). Anti-inflammatory drugs, includingbut not limited to nonsteroidal anti-inflammatory drugs andcorticosteroids, and antiviral drugs, including but not limited toribivirin, vidarabine, acyclovir and ganciclovir, may also be combinedin compositions featured in the invention. See, generally, The MerckManual of Diagnosis and Therapy, 15th Ed., Berkow et al., eds., 1987,Rahway, N.J., pages 2499-2506 and 46-49, respectively). Other non-RNAichemotherapeutic agents are also within the scope of this invention. Twoor more combined compounds may be used together or sequentially.

Toxicity and therapeutic efficacy of such compounds can be determined bystandard pharmaceutical procedures in cell cultures or experimentalanimals, e.g., for determining the LD50 (the dose lethal to 50% of thepopulation) and the ED50 (the dose therapeutically effective in 50% ofthe population). The dose ratio between toxic and therapeutic effects isthe therapeutic index and it can be expressed as the ratio LD50/ED50.Compounds that exhibit high therapeutic indices are typical.

The data obtained from cell culture assays and animal studies can beused in formulation a range of dosage for use in humans. The dosage ofcompositions featured in the invention lies generally within a range ofcirculating concentrations that include the ED50 with little or notoxicity. The dosage may vary within this range depending upon thedosage form employed and the route of administration utilized. For anycompound used in the methods featured in the invention, thetherapeutically effective dose can be estimated initially from cellculture assays. A dose may be formulated in animal models to achieve acirculating plasma concentration range of the compound or, whenappropriate, of the polypeptide product of a target sequence (e.g.,achieving a decreased concentration of the polypeptide) that includesthe IC50 (i.e., the concentration of the test compound which achieves ahalf-maximal inhibition of symptoms) as determined in cell culture. Suchinformation can be used to more accurately determine useful doses inhumans. Levels in plasma may be measured, for example, by highperformance liquid chromatography.

In addition to their administration, as discussed above, the dsRNAsfeatured in the invention can be administered in combination with otherknown agents effective in treatment of pathological processes mediatedby XBP-1 expression. In any event, the administering physician canadjust the amount and timing of dsRNA administration on the basis ofresults observed using standard measures of efficacy known in the art ordescribed herein.

Methods for Treating Diseases Caused by Expression of the XBP-1 Gene

The invention relates in particular to the use of a dsRNA targetingXBP-1 and compositions containing at least one such dsRNA, for thetreatment of an XBP-1-mediated disorder or disease. For example, a dsRNAtargeting an XBP-1 gene can be useful for the treatment of a metabolicdisease, such as Type II diabetes and metabolic syndrome, or acardiovascular disease. “Metabolic syndrome” (also called metabolicsyndrome X, X syndrome, insulin resistance syndrome, Reaven's syndrome,and CHAOS) is characterized by a group of metabolic risk factorsincluding: abdominal obesity (excessive fat tissue in and around theabdomen), atherogenic dyslipidemia (blood fat disorders (including hightriglycerides, low HDL cholesterol and high LDL cholesterol) that fosterplaque build-up in artery walls), elevated blood pressure, insulinresistance or glucose intolerance (due to the body's inability toproperly use insulin or blood sugar), a prothrombotic state (e.g., highfibrinogen or plasminogen activator inhibitor-1 in the blood), and aproinflammatory state (e.g., elevated C-reactive protein in the blood).People with metabolic syndrome are at increased risk of coronary heartdisease and other diseases related to plaque buildups in artery walls(e.g., stroke and peripheral vascular disease), and Type II diabetes. A“cardiovascular disease,” as used herein is a disorder that affects theheart or blood vessels, such as atherosclerosis, coronary arterydisease, high blood pressure, congenital heart disease, aneurysm, aheart valve disease, a heart infection, or cardiomyopathy. Othermetabolic diseases suitable for treatment with a dsRNA targeting XBP-1include obesity and insulin resistance.

A dsRNA targeting XBP-1 is also useful for the treatment of adyslipidemia, such as a hyperlidipemia (e.g., hypercholesterolemia), ora disorder associated with a dyslipidemia, such as atherosclerosis. A“hyperlipidemia” refers to elevated lipid levels in the blood (e.g., inplasma), such as elevated levels of one or more of cholesterol, LDL (lowdensity lipoprotein), VLDL (very low density lipoprotein),triglycerides, or chylomicrons.

A dsRNA targeting XBP-1 is also useful for the treatment of liverdisorders, such as a nonalcoholic fatty liver disease (NAFLD), which isa fatty inflammation of the liver not due to excessive use of alcohol,or cirrhosis. For example, a dsRNA targeting XBP-1 can be used to treatnon-alcoholic steatohepatitis (NASH), which is one of the most extremeforms of NAFLD, and which is regarded as a major cause of cirrhosis ofthe liver of unknown cause.

A dsRNA targeting XBP-1 can also be useful for the treatment of cancer,such as a leukemia, e.g., ATLL. A dsRNA targeting XBP-1 can also be usedto treat a myelopathy, e.g., tropical spastic paresis (TSP). TSP is achronic and progressive disease of the nervous system that typicallyaffects adults living in equatorial areas of the world and can causeprogressive weakness, stiff muscles, muscle spasms, sensory disturbance,and sphincter dysfunction. A “myelopathy,” as used herein, is aneurological deficit related to the spinal cord.

A composition containing a dsRNA targeting XBP-1 may also be used totreat other tumors and cancers, such as breast cancer, lung cancer, headand neck cancer, brain cancer, abdominal cancer, colon cancer,colorectal cancer, esophagus cancer, gastrointestinal cancer, glioma,tongue cancer, neuroblastoma, osteosarcoma, ovarian cancer, pancreaticcancer, prostate cancer, retinoblastoma, Wilm's tumor, multiple myelomaand for the treatment of skin cancer, like melanoma, for the treatmentof lymphomas and blood cancer.

Owing to the inhibitory effects on XBP-1 expression, a compositionaccording to the invention or a pharmaceutical composition preparedtherefrom can enhance the quality of life.

The invention further relates to the use of a dsRNA or a pharmaceuticalcomposition thereof, e.g., for treating a metabolic disorder,cardiovascular disease, or an HTLV-1 mediated disorder, in combinationwith other pharmaceuticals and/or other therapeutic methods, e.g., withknown pharmaceuticals and/or known therapeutic methods, such as, forexample, those which are currently employed for treating these disorder.In one example, administration of a dsRNA targeting XBP-1 can beaccompanied by a exercise regimen or by dietary restrictions. A dsRNAfeatured in the invention can also be administered with a drug orcombination of drugs for managing Type II diabetes, e.g., asulfonylurea, a biguanide, an alpha-glucosidase inhibitor, athiazolidinedione (e.g., rosiglitazone or pioglitazone), a meglitinide,a D-phenylalanine derivative, an amylin synthetic derivatives, anincretin mimetic, metformin, or an insulin. Exemplary insulins includeregular insulins (Humulin®, Novolin®), insulin lispro (Humalog®),insulin aspart (Novolog®), insulin glulisine (Apidra®), prompt insulinzinc (Semilente®, slightly slower acting), inhaled insulin (Exubera®),intermediate-acting insulins, isophane insulin, neutral protamineHagedorn (NPH), insulin zinc (Lente®), extended insulin zinc insulin(Ultralente®), insulin glargine (Lantus®), and insulin detemir(Levemir®).

In another example, a composition containing a dsRNA targeting XBP-1 isadministered in combination with a lipid-lowering drug, such as astatin, e.g., atorvastatin (Lipitor®) or simvastatin (Mevacor®);ezetimibe (Zetia®); a bile-acid sequestrant, such as Questran®; afibrate, such as gemfibrozil (Lopid®) or fenofibrate (Tricor); or acompound that raises HDL levels, such as nicotinic acid (Niacin).

A dsRNA targeting XBP-1 can also be provided in combination with avitamin, such as vitamin E or vitamin C, e.g., for treatment of a liverdisorder, such as NAFLD or NASH.

In another example, a composition containing a dsRNA targeting XBP-1 isadministered in combination with an antiviral drug, such as zidovudine,ribivirin, vidarabine, acyclovir and ganciclovir, or ananti-inflammatory drug, such as a nonsteroidal anti-inflammatory drugsor corticosteroid. See, generally, The Merck Manual of Diagnosis andTherapy, 15th Ed., Berkow et al., eds., 1987, Rahway, N.J., pages2499-2506 and 46-49, respectively). Administraton can also be incombination with an interferon, such as interferon alpha or interferonbeta; lioresal, tizanidine, or oxybutynin.

In certain embodiments, administration is with a chemotherapy agent,such as deoxycoformycin, cisplatin, cyclophosphamide, 5-fluorouracil,adriamycin, daunorubicin, tamoxifen aunorubicin, daunomycin,dactinomycin, doxorubicin, epirubicin, idarubicin, esorubicin,bleomycin, mafosfamide, ifosfamide, cytosine arabinoside,bis-chloroethylnitrosurea, busulfan, mitomycin C, actinomycin D,mithramycin, prednisone, hydroxyprogesterone, testosterone, tamoxifen,dacarbazine, procarbazine, hexamethylmelamine, pentamethylmelamine,mitoxantrone, amsacrine, chlorambucil, methylcyclohexylnitrosurea,nitrogen mustards, melphalan, cyclophosphamide, 6-mercaptopurine,6-thioguanine, cytarabine, 5-azacytidine, hydroxyurea, deoxycoformycin,4-hydroxyperoxycyclophosphoramide, 5-fluorouracil (5-FU),5-fluorodeoxyuridine (5-FUdR), methotrexate (MTX), colchicine, taxol,vincristine, vinblastine, etoposide (VP-16), trimeterxate, irinotecan,topotecan, gemcitabine, teniposide, cisplatin and diethylstilbestrol(DES). See, generally, The merck Manual of Diagnosis and Therapy, 15thEd. 1987, pp. 1206-1228, Berkow et al., eds., Rahway, N.J. When usedwith the dsRNAs featured in the invention, such chemotherapeutic agentsmay be used individually (e.g., deoxycoformycin and dsRNA), sequentially(e.g., antiviral and dsRNA for a period of time, followed bydeoxycoformycin and dsRNA), or in combination with one or more othersuch agents (e.g., deoxycoformycin, antiviral and dsRNA, ordeoxycoformycin, radiotherapy and dsRNA). Two or more combined compoundsmay be used together or sequentially.

Patients can be administered a therapeutic amout of dsRNA, such as 0.02,0.1, 0.5 mg/kg, 1.0 mg/kg, 1.5 mg/kg, 2.0 mg/kg, or 2.5 mg/kg dsRNA. ThedsRNA can be administered by intravenous infusion over a period of time,such as over a 5 minute, 10 minute, 15 minute, 20 minute, or 25 minuteperiod. In some embodiments, the administration is repeated, forexample, on a regular basis, such as biweekly (i.e., every two weeks)for one month, two months, three months, four months or longer. After aninitial treatment regimen, the treatments can be administered on a lessfrequent basis. For example, after administration biweekly for threemonths, administration can be repeated once per month, for six months ora year or longer. Administration of the dsRNA can reduce LDL levels inthe blood of the patient by at least 20%, 25%, 30%, 40%, 50%, 60%, 70%,80% or 90% or more.

Before administration of a full dose of a dsRNA targeting XBP-1, apatient can be administered a smaller dose, such as a 5% infusionreaction, and monitored for adverse effects, such as an allergicreaction. In another example, the patient can be monitored for unwantedimmunostimulatory effects, such as increased cytokine (e.g., TNF-alphaor INF-alpha) levels.

Many XBP-1-associated diseases and disorders are hereditary. Therefore,a patient in need of a dsRNA targeting XBP-1 can be identified by takinga family history. A healthcare provider, such as a doctor, nurse, orfamily member, can take a family history before prescribing oradministering a dsRNA. A DNA test may also be performed on the patientto identify a mutation in the target gene, before a dsRNA isadministered to the patient.

Methods for Inhibiting Expression of the XBP-1 Gene

In yet another aspect, the invention provides a method for inhibitingthe expression of an XBP-1 gene in a mammal. The method includesadministering a composition featured in the invention to the mammal suchthat expression of the target XBP-1 gene is silenced.

When the organism to be treated is a mammal such as a human, thecomposition may be administered by any means known in the art including,but not limited to oral or parenteral routes, including intravenous,intramuscular, subcutaneous, transdermal, airway (aerosol), nasal,rectal, and topical (including buccal and sublingual) administration. Incertain embodiments, the compositions are administered by intravenousinfusion or injection.

Unless otherwise defined, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Although methods and materialssimilar or equivalent to those described herein can be used in thepractice or testing of the dsRNAs and methods featured in the invention,suitable methods and materials are described below. All publications,patent applications, patents, and other references mentioned herein areincorporated by reference in their entirety. In case of conflict, thepresent specification, including definitions, will control. In addition,the materials, methods, and examples are illustrative only and notintended to be limiting.

EXAMPLES Example 1 dsRNA Synthesis

Source of Reagents

Where the source of a reagent is not specifically given herein, suchreagent may be obtained from any supplier of reagents for molecularbiology at a quality/purity standard for application in molecularbiology.

siRNA Synthesis

Single-stranded RNAs were produced by solid phase synthesis on a scaleof 1 μmole using an Expedite 8909 synthesizer (Applied Biosystems,Applera Deutschland GmbH, Darmstadt, Germany) and controlled pore glass(CPG, 500 Å, Proligo Biochemie GmbH, Hamburg, Germany) as solid support.RNA and RNA containing 2′-O-methyl nucleotides were generated by solidphase synthesis employing the corresponding phosphoramidites and2′-O-methyl phosphoramidites, respectively (Proligo Biochemie GmbH,Hamburg, Germany). These building blocks were incorporated at selectedsites within the sequence of the oligoribonucleotide chain usingstandard nucleoside phosphoramidite chemistry such as described inCurrent protocols in nucleic acid chemistry, Beaucage, S. L. et al.(Edrs.), John Wiley & Sons, Inc., New York, N.Y., USA. Phosphorothioatelinkages were introduced by replacement of the iodine oxidizer solutionwith a solution of the Beaucage reagent (Chruachem Ltd, Glasgow, UK) inacetonitrile (1%). Further ancillary reagents were obtained fromMallinckrodt Baker (Griesheim, Germany).

Deprotection and purification of the crude oligoribonucleotides by anionexchange HPLC were carried out according to established procedures.Yields and concentrations were determined by UV absorption of a solutionof the respective RNA at a wavelength of 260 nm using a spectralphotometer (DU 640B, Beckman Coulter GmbH, UnterschleiBheim, Germany).Double stranded RNA was generated by mixing an equimolar solution ofcomplementary strands in annealing buffer (20 mM sodium phosphate, pH6.8; 100 mM sodium chloride), heated in a water bath at 85-90° C. for 3minutes and cooled to room temperature over a period of 3-4 hours. Theannealed RNA solution was stored at −20° C. until use.

For the synthesis of 3′-cholesterol-conjugated siRNAs (herein referredto as -Chol-3′), an appropriately modified solid support is used for RNAsynthesis. The modified solid support is prepared as follows:

Diethyl-2-azabutane-1,4-dicarboxylate AA

A 4.7 M aqueous solution of sodium hydroxide (50 mL) is added into astirred, ice-cooled solution of ethyl glycinate hydrochloride (32.19 g,0.23 mole) in water (50 mL). Then, ethyl acrylate (23.1 g, 0.23 mole) isadded and the mixture stirred at room temperature until completion ofthe reaction is ascertained by TLC. After 19 h the solution ispartitioned with dichloromethane (3×100 mL). The organic layer is driedwith anhydrous sodium sulfate, filtered and evaporated. The residue isdistilled to afford AA (28.8 g, 61%).

3-{Ethoxycarbonylmethyl-[6-(9H-fluoren-9-ylmethoxycarbonyl-amino)-hexanoyl]-amino}-propionicacid ethyl ester AB

Fmoc-6-amino-hexanoic acid (9.12 g, 25.83 mmol) is dissolved indichloromethane (50 mL) and cooled with ice. Diisopropylcarbodiimde(3.25 g, 3.99 mL, 25.83 mmol) is added to the solution at 0° C. This isfollowed by the addition of Diethyl-azabutane-1,4-dicarboxylate (5 g,24.6 mmol) and dimethylamino pyridine (0.305 g, 2.5 mmol). The solutionis brought to room temperature and stirred further for 6 h. Completionof the reaction is ascertained by TLC. The reaction mixture isconcentrated under vacuum and ethyl acetate is added to precipitatediisopropyl urea. The suspension is filtered. The filtrate is washedwith 5% aqueous hydrochloric acid, 5% sodium bicarbonate and water. Thecombined organic layer is dried over sodium sulfate and concentrated togive the crude product which is purified by column chromatography (50%EtOAC/Hexanes) to yield 11.87 g (88%) of AB.

3-[(6-Amino-hexanoyl)-ethoxycarbonylmethyl-amino]-propionic acid ethylester AC

3-{Ethoxycarbonylmethyl-[6-(9H-fluoren-9-ylmethoxycarbonylamino)-hexanoyl]-amino}-propionicacid ethyl ester AB (11.5 g, 21.3 mmol) is dissolved in 20% piperidinein dimethylformamide at 0° C. The solution is continued stirring for 1h. The reaction mixture is concentrated under vacuum, water is added tothe residue, and the product is extracted with ethyl acetate. The crudeproduct is purified by conversion into its hydrochloride salt.

3({6-[17-(1,5-Dimethyl-hexyl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yloxycarbonylamino]-hexanoyl}ethoxycarbonylmethyl-amino)-propionicacid ethyl ester AD

The hydrochloride salt of3-[(6-Amino-hexanoyl)-ethoxycarbonylmethyl-amino]-propionic acid ethylester AC (4.7 g, 14.8 mmol) is taken up in dichloromethane. Thesuspension is cooled to 0° C. on ice. Diisopropylethylamine (3.87 g, 5.2mL, 30 mmol) is added to the suspension. To the resulting solution,cholesteryl chloroformate (6.675 g, 14.8 mmol) is added. The reactionmixture is stirred overnight. The reaction mixture is diluted withdichloromethane and washed with 10% hydrochloric acid. The product ispurified by flash chromatography (10.3 g, 92%).

1-{6-[17-(1,5-Dimethyl-hexyl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yloxycarbonylamino]-hexanoyl}-4-oxo-pyrrolidine-3-carboxylicacid ethyl ester AE

Potassium t-butoxide (1.1 g, 9.8 mmol) is slurried in 30 mL of drytoluene. The mixture is cooled to 0° C. on ice, and 5 g (6.6 mmol) ofdiester AD is added slowly with stirring within 20 mins. The temperatureis kept below 5° C. during the addition. The stifling is continued for30 mins at 0° C., and 1 mL of glacial acetic acid is added, immediatelyfollowed by 4 g of NaH₂PO₄.H₂O in 40 mL of water. The resultant mixtureis extracted twice with 100 mL of dichloromethane each, and the combinedorganic extracts are washed twice with 10 mL of phosphate buffer each,dried, and evaporated to dryness. The residue is dissolved in 60 mL oftoluene, cooled to 0° C. and extracted with three 50 mL portions of coldpH 9.5 carbonate buffer. The aqueous extracts are adjusted to pH 3 withphosphoric acid, and extracted with five 40 mL portions of chloroformwhich are combined, dried and evaporated to dryness. The residue ispurified by column chromatography using 25% ethylacetate/hexane toafford 1.9 g of b-ketoester (39%).

[6-(3-Hydroxy-4-hydroxymethyl-pyrrolidin-1-yl)-6-oxo-hexyl]-carbamicacid17-(1,5-dimethyl-hexyl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-ylester AF

Methanol (2 mL) is added dropwise over a period of 1 h to a refluxingmixture of b-ketoester AE (1.5 g, 2.2 mmol) and sodium borohydride(0.226 g, 6 mmol) in tetrahydrofuran (10 mL). Stirring is continued atreflux temperature for 1 h. After cooling to room temperature, 1 N HCl(12.5 mL) is added, the mixture is extracted with ethylacetate (3×40mL). The combined ethylacetate layer is dried over anhydrous sodiumsulfate and concentrated under vacuum to yield the product which ispurified by column chromatography (10% MeOH/CHCl₃) (89%).

(6-{3-[Bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-4-hydroxy-pyrrolidin-1-yl}-6-oxo-hexyl)-carbamicacid17-(1,5-dimethyl-hexyl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-ylester AG

Diol AF (1.25 gm 1.994 mmol) is dried by evaporating with pyridine (2×5mL) in vacuo. Anhydrous pyridine (10 mL) and4,4′-dimethoxytritylchloride (0.724 g, 2.13 mmol) are added withstirring. The reaction is carried out at room temperature overnight. Thereaction is quenched by the addition of methanol. The reaction mixtureis concentrated under vacuum and dichloromethane (50 mL) is added to theresidue. The organic layer is washed with 1M aqueous sodium bicarbonate.The organic layer is dried over anhydrous sodium sulfate, filtered andconcentrated. The residual pyridine is removed by evaporating withtoluene. The crude product is purified by column chromatography (2%MeOH/Chloroform, Rf=0.5 in 5% MeOH/CHCl₃) (1.75 g, 95%).

Succinic acidmono-(4-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-1-{6-[17-(1,5-dimethyl-hexyl)-10,13-dimethyl2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1Hcyclopenta[a]phenanthren-3-yloxycarbonylamino]-hexanoyl}-pyrrolidin-3-yl)esterAH

Compound AG (1.0 g, 1.05 mmol) is mixed with succinic anhydride (0.150g, 1.5 mmol) and DMAP (0.073 g, 0.6 mmol) and dried in a vacuum at 40°C. overnight. The mixture is dissolved in anhydrous dichloroethane (3mL), triethylamine (0.318 g, 0.440 mL, 3.15 mmol) is added and thesolution is stirred at room temperature under argon atmosphere for 16 h.It is then diluted with dichloromethane (40 mL) and washed with ice coldaqueous citric acid (5 wt %, 30 mL) and water (2×20 mL). The organicphase is dried over anhydrous sodium sulfate and concentrated todryness. The residue is used as such for the next step.

Cholesterol Derivatised CPG AI

Succinate AH (0.254 g, 0.242 mmol) is dissolved in a mixture ofdichloromethane/acetonitrile (3:2, 3 mL). To that solution, DMAP (0.0296g, 0.242 mmol) in acetonitrile (1.25 mL),2,2′-Dithio-bis(5-nitropyridine) (0.075 g, 0.242 mmol) inacetonitrile/dichloroethane (3:1, 1.25 mL) are added successively. Tothe resulting solution triphenylphosphine (0.064 g, 0.242 mmol) inacetonitrile (0.6 ml) is added. The reaction mixture turns bright orangein color. The solution is agitated briefly using a wrist-action shaker(5 mins). Long chain alkyl amine-CPG (LCAA-CPG) (1.5 g, 61 mM) is added.The suspension is agitated for 2 h. The CPG is filtered through asintered funnel and washed with acetonitrile, dichloromethane and ethersuccessively. Unreacted amino groups are masked using aceticanhydride/pyridine. The achieved loading of the CPG was measured bytaking UV measurement (37 mM/g).

The synthesis of siRNAs bearing a 5′-12-dodecanoic acid bisdecylamidegroup (herein referred to as “5′-C32-”) or a 5′-cholesteryl derivativegroup (herein referred to as “5′-Chol-”) is performed as described in WO2004/065601, except that, for the cholesteryl derivative, the oxidationstep is performed using the Beaucage reagent in order to introduce aphosphorothioate linkage at the 5′-end of the nucleic acid oligomer.

Nucleic acid sequences are represented below using standardnomenclature, and specifically the abbreviations of Table 1.

TABLE 1 Abbreviations of nucleotide monomers used in nucleic acidsequence representation. It will be understood that these monomers, whenpresent in an oligonucleotide, are mutually linked by5′-3′-phosphodiester bonds. Abbreviation^(a) Nucleotide(s) A Adenosine CCytidine G Guanosine T thymidine U uridine N any nucleotide (G, A, C, U,or T) a 2′-O-methyladenosine c 2′-O-methylcytidine g2′-O-methylguanosine u 2′-O-methyluridine sT phosphorothioate linkage

Example 2 Synthesis of XBP-1 dsRNAs

XBP-1 sequences were synthesized on MerMade 192 synthesizer at 1 μmolscale.

For all the sequences in Table 2, ‘endolight’ chemistry was applied asshown below and in Table 4.

-   -   All pyrimidines (cytosine and uridine) in the sense strand were        replaced with corresponding 2′-O-Methyl bases (2′ O-Methyl C and        2′-O-Methyl U)    -   In the antisense strand, pyrimidines adjacent to(towards 5′        position) ribo A nucleoside were replaced with their        corresponding 2-O-Methyl nucleosides    -   A two base dTsdT extension at 3′ end of both sense and anti        sense sequences was introduced    -   The sequence file was converted to a text file to make it        compatible for loading in the MerMade 192 synthesis software

Solid supported oligonucleotide synthesis using phosphoramiditechemistry was performed to synthesize the XBP-1 sequences.

TABLE 2 Exemplary XBP-1 dsRNAs SEQ SEQ ID ID OligoName NO: sense (5′-3′)NO: antisense (5′-3′) NM_001004210_1128-1146 2127 CCCAGCUGAUUAGUGUCUA2128 UAGACACUAAUCAGCUGGG NM_001004210_1129-1147 2129 CCAGCUGAUUAGUGUCUAA2130 UUAGACACUAAUCAGCUGG NM_001004210_677-695 2131 CUCCCAGAGGUCUACCCAG2132 CUGGGUAGACCUCUGGGAG NM_001004210_893-911 2133 GAUCACCCUGAAUUCAUUG2134 CAAUGAAUUCAGGGUGAUC NM_001004210_895-913 2135 UCACCCUGAAUUCAUUGUC2136 GACAAUGAAUUCAGGGUGA NM_001004210_1127-1145 2137 CCCCAGCUGAUUAGUGUCU2138 AGACACUAAUCAGCUGGGG NM_001004210_894-912 2139 AUCACCCUGAAUUCAUUGU2140 ACAAUGAAUUCAGGGUGAU NM_001004210_1760-1778 2141 CAUUUAUUUAAAACUACCC2142 GGGUAGUUUUAAAUAAAUG NM_001004210_215-233 2143 ACUGAAAAACAGAGUAGCA2144 UGCUACUCUGUUUUUCAGU NM_001004210_1759-1777 2145 CCAUUUAUUUAAAACUACC2146 GGUAGUUUUAAAUAAAUGG NM_001004210_367-385 2147 UUGAGAACCAGGAGUUAAG2148 CUUAACUCCUGGUUCUCAA NM_001004210_896-914 2149 CACCCUGAAUUCAUUGUCU2150 AGACAAUGAAUUCAGGGUG NM_001004210_214-232 2151 AACUGAAAAACAGAGUAGC2152 GCUACUCUGUUUUUCAGUU NM_001004210_216-234 2153 CUGAAAAACAGAGUAGCAG2154 CUGCUACUCUGUUUUUCAG XM_001103095_387-405 1 AGAAAAUCAGCUUUUACGA 2UCGUAAAAGCUGAUUUUCU XM_001103095_1151-1169 3 UCCCCAGCUGAUUAGUGUC 4GACACUAAUCAGCUGGGGA XM_001103095_1466-1484 5 UACUUAUUAUGUAAGGGUC 6GACCCUUACAUAAUAAGUA XM_001103095_1435-1453 7 UAUCUUAAAAGGGUGGUAG 8CUACCACCCUUUUAAGAUA XM_001103095_577-595 9 CCAUGGAUUCUGGCGGUAU 10AUACCGCCAGAAUCCAUGG XM_001103095_790-808 11 UUAAUGAACUAAUUCGUUU 12AAACGAAUUAGUUCAUUAA XM_001103095_1479-1497 13 AGGGUCAUUAGACAAAUGU 14ACAUUUGUCUAAUGACCCU XM_001103095_794-812 15 UGAACUAAUUCGUUUUGAC 16GUCAAAACGAAUUAGUUCA XM_001103095_1150-1168 23 UUCCCCAGCUGAUUAGUGU 24ACACUAAUCAGCUGGGGAA XM_001103095_1473-1491 25 UAUGUAAGGGUCAUUAGAC 26GUCUAAUGACCCUUACAUA

The synthesis of the sequences in Tables 2 and 4 was performed at 1 μmscale in 96-well plates. The amidite solutions were prepared at 0.1Mconcentration and ethyl thio tetrazole (0.6M in acetonitrile) was usedas an activator.

The synthesized sequences were cleaved and deprotected in 96-wellplates, using methylamine in the first step and pyradine.3HF in thesecond step. The crude sequences thus obtained were precipitated usingan acetone:ethanol mix, and the pellets were resuspended in 0.5M sodiumacetate buffer. Samples from each sequence were analyzed by LC-MS andthe resulting mass data confirmed the identity of the sequences. Aselected set of samples was also analyzed by IEX chromatography.

The sequences were purified on an AKTA explorer purification systemusing a Source Q column. A single peak corresponding to the full lengthsequence was collected in the eluent and was subsequently analyzed forpurity by ion exchange chromatography.

The purified sequences were desalted on a Sephadex G25 column using anAKTA purifier. The desalted XBP-1 sequences were analyzed forconcentration and purity. The single strands were then submitted forannealing.

TABLE 3 XBP-1 oligos with Endolight Chemistry Modifications Speciesspecificity and target sequence Duplex from 5′ to 3′ on Oligo name Oligoname Name mRNA transcript Sense Antisense AD18027 NM_001004210_1128-1146A-31668 A-31669 AD18028 NM_001004210_1129-1147 A-31670 A-31671 AD18029NM_001004210_677-695 A-31672 A-31673 AD18030 NM_001004210_893-911A-31674 A-31675 AD18031 NM_001004210_895-913 A-31676 A-31677 AD18032NM_001004210_1127-1145 A-31678 A-31679 AD18033 NM_001004210_894-912A-31680 A-31681 AD18034 NM_001004210_1760-1778 A-31682 A-31683 AD18035NM_001004210_215-233 A-31684 A-31685 AD18036 NM_001004210_1759-1777A-31686 A-31687 AD18037 NM_001004210_367-385 A-31688 A-31689 AD18038NM_001004210_896-914 A-31690 A-31691 AD18039 NM_001004210_214-232A-31692 A-31693 AD18040 NM_001004210_216-234 A-31694 A-31695 AD18041XM_001103095_387-405 A-31696 A-31697 AD18042 XM_001103095_1151-1169A-31698 A-31699 AD18043 XM_001103095_1466-1484 A-31700 A-31701 AD18044XM_001103095_1435-1453 A-31702 A-31703 AD18045 XM_001103095_577-595A-31704 A-31705 AD18046 XM_001103095_790-808 A-31706 A-31707 AD18047XM_001103095_1479-1497 A-31708 A-31709 AD18048 XM_001103095_794-812A-31710 A-31711 AD18049 XM_001103095_1150-1168 A-31712 A-31713 AD18050XM_001103095_1473-1491 A-31714 A-31715

TABLE 4 XBP-1 sequences with Endolight chemistry modifications Oligo SEQOligo SEQ name ID name ID Sense NO: Sense (5′-3′) Antisense NO:Antisense (5′-3′) A-31668 2155 cccAGcuGAuuAGuGucuAdTsdT A-31669 2156uAGAcACuAAUcAGCUGGGdTsdT A-31670 2157 ccAGcuGAuuAGuGucuAAdTsdT A-316712158 UuAGAcACuAAUcAGCUGGdTsdT A-31672 2159 cucccAGAGGucuAcccAGdTsdTA-31673 2160 CUGGGuAGACCUCUGGGAGdTsdT A-31674 2161GAucAcccuGAAuucAuuGdTsdT A-31675 2162 cAAUGAAUUcAGGGUGAUCdTsdT A-316762163 ucAcccuGAAuucAuuGucdTsdT A-31677 2164 GAcAAUGAAUUcAGGGUGAdTsdTA-31678 2165 ccccAGcuGAuuAGuGucudTsdT A-31679 2166AGAcACuAAUcAGCUGGGGdTsdT A-31680 2167 AucAcccuGAAuucAuuGudTsdT A-316812168 AcAAUGAAUUcAGGGUGAUdTsdT A-31682 2169 cAuuuAuuuAAAAcuAcccdTsdTA-31683 2170 GGGuAGUUUuAAAuAAAUGdTsdT A-31684 2171AcuGAAAAAcAGAGuAGcAdTsdT A-31685 2172 UGCuACUCUGUUUUUcAGUdTsdT A-316862173 ccAuuuAuuuAAAAcuAccdTsdT A-31687 2174 GGuAGUUUuAAAuAAAUGGdTsdTA-31688 2175 uuGAGAAccAGGAGuuAAGdTsdT A-31689 2176CUuAACUCCUGGUUCUcAAdTsdT A-31690 2177 cAcccuGAAuucAuuGucudTsdT A-316912178 AGAcAAUGAAUUcAGGGUGdTsdT A-31692 2179 AAcuGAAAAAcAGAGuAGcdTsdTA-31693 2180 GCuACUCUGUUUUUcAGUUdTsdT A-31694 2181cuGAAAAAcAGAGuAGcAGdTsdT A-31695 2182 CUGCuACUCUGUUUUUcAGdTsdT A-316962183 AGAAAAucAGcuuuuAcGAdTsdT A-31697 2184 UCGuAAAAGCUGAUUUUCUdTsdTA-31698 2185 uccccAGcuGAuuAGuGucdTsdT A-31699 2186GAcACuAAUcAGCUGGGGAdTsdT A-31700 2187 uAcuuAuuAuGuAAGGGucdTsdT A-317012188 GACCCUuAcAuAAuAAGuAdTsdT A-31702 2189 uAucuuAAAAGGGuGGuAGdTsdTA-31703 2190 CuACcACCCUUUuAAGAuAdTsdT A-31704 2191ccAuGGAuucuGGcGGuAudTsdT A-31705 2192 AuACCGCcAGAAUCcAUGGdTsdT A-317062193 uuAAuGAAcuAAuucGuuudTsdT A-31707 2194 AAACGAAUuAGUUcAUuAAdTsdTA-31708 2195 AGGGucAuuAGAcAAAuGudTsdT A-31709 2196AcAUUUGUCuAAUGACCCUdTsdT A-31710 2197 uGAAcuAAuucGuuuuGAcdTsdT A-317112198 GUcAAAACGAAUuAGUUcAdTsdT A-31712 2199 uuccccAGcuGAuuAGuGudTsdTA-31713 2200 AcACuAAUcAGCUGGGGAAdTsdT A-31714 2201uAuGuAAGGGucAuuAGAcdTsdT A-31715 2202 GUCuAAUGACCCUuAcAuAdTsdT

Example 3 Single Concentration Silencing Experiment (% KnockdownRelative to Control 12 nM)

Transfection of PC-3 cells was performed in 6-well plates: 31.25 μl (for12.5 nM) of 200 nM duplex was added to 500 μl Opti-MEM (Invitrogen,Carlsbad, Calif.) in a well of a 6-well plate. 5 μl Lipofectamine™RNAiMAX (Invitrogen, Carlsbad, Calif.) was added to the wells, mixed andincubated for 15 minutes. 2.0 ml complete growth media withoutAntibiotics containing 0.6×10⁵ cells was added, and the misture wasmixed by rocking back and forth for 36 hours. Total RNA was isolatedusing Qiagen RNeasy kit (Qiagen, Valencia, Calif.) according to themanufacturer's instructions. RNA concentration was measured using ananodrop and was diluted to 2 μg per 10 μl.

cDNA was synthesized using an ABI High-capacity cDNA reversetranscription kit (Applied Biosystems, Foster City, Calif.) and 2 μgtotal RNA. Quantitative PCR (qPCR) was performed using probes to amplifyXBP-1 and 18S in the same reaction. All reactions were performed intriplicate.

qPCR data were analyzed using the ΔΔCt method using BlockiT™ fluorescentOligo (Invitrogen, Carlsbad, Calif.), which does not target any humangene, as a negative control.

Generation of IC50s (for AD18028, AD18029, AD18037, AD18038, AD18040)

IC50s were generated for the 5 duplexes that showed the best silencingin the single concentration experiment.

Three sets of transfections were performed in two independentexperiments using the dsRNAs shown in Table 4. In the first experiment,qPCR experiment 1 (qPCR1) and branched DNA (bDNA) results were obtainedfrom different transfections that were done in parallel using the samecells and reagents. In the second experiment, qPCR2 results weregenerated from transfections that were done under the same conditions asthe first experiment.

Transfection of PC-3 cells was performed in 96-well plates. The duplexconcentrations tested were 50 nM, 10 nM, 5 nM, 1 nM, 0.5 nM, 0.1 nM,0.05 nM, 0.01 nM, 0.005 nM, 0.001 nM, 0.0005 nM, and 0.0001 nM. EachdsRNA was diluted so that 5 μl would be added to 100 μl for eachtransfection to give the desired concentration. Transfections wereperformed using Opti-MEM and lipofectamine, and then cultured in EMEM.

RNA was extracted using an RNAqueous 96 kit (Applied Biosystems/Ambion,Austin, Tex.) according to manufactures instructions.

cDNA synthesis and qPCR were done as described above, and qPCR data wereanalyzed using the ΔΔCt method using AD-3966 as a control, which targetsthe Sid1 gene but has been shown to have no activity in cell basedassays.

Branched DNA assays were performed usint QuantiGene® 2.0 (Panomics,Fremont, Calif.). The bDNA data were analyzed by subtracting the averagebackground from each triplicate sample, averaging the triplicate GAPDH(control probe) and TTR (experimental probe) then taking the ratio:

(experimental probe-background)/(control probe-background).

The results are shown in Tables 5 and 6.

TABLE 5 IC50 results for XBP-1 dsRNA IC50 Human Mouse Rat Rhesus IC50(nM) IC50 (nM) (nM) oligoName antisScore antisScore antisScoreantisScore qPCR 1 qPCR 2 bDNA AD18027 3 2 3 3 AD18028 3 2 3.2 3 0.0190.011 0.034 AD18029 3 1.2 2.8 3 0.03 0.020 0.026 AD18030 3 2 1 2 AD180313 2 3 2.2 AD18032 3 2.2 3 2.8 AD18033 3 3 2.8 2 AD18034 2.2 2 2.8 2AD18035 2.2 2 2 2.4 AD18036 2.2 2 2 2 AD18037 2.2 2 2 2.2 0.016 0.0190.016 AD18038 2.2 2 3 2.2 0.004 0.003 0.006 AD18039 2.2 3 2 2.2 AD180402.2 2 2 2 0.057 0.052 0.065 AD18041 4 NH NH 3.4 AD18042 4 NH NH 3.2AD18043 4 NH NH 3 AD18044 3.2 NH NH 3.2 AD18045 3.2 NH NH 3.2 AD180463.2 NH NH 3.2 AD18047 3.2 NH NH 3 AD18048 3.2 NH NH 3 AD18049 3 NH NH3.2 AD18050 3 NH NH 3.2 NH = No homology; bold = perfect match withhamster

TABLE 6 XBP-1 Silencing Data % knockdown relative to control IC50 IC50IC50 (12 nM) (nM) (nM) (nM) oligoName (36 hours) qPCR 1 qPCR 2 bDNAAD18027 81.993 AD18028 90.581 0.019 0.011 0.034 AD18029 97.749 0.03 0.020.026 AD18030 82.845 AD18031 34.782 AD18032 84.893 AD18033 68.971AD18034 42.962 AD18035 82.076 AD18036 77.26 AD18037 94.209 0.016 0.0190.016 AD18038 93.239 0.004 0.003 0.006 AD18039 56.873 AD18040 93.750.057 0.052 0.065 AD18041 84.396 AD18042 ND AD18043 27.804 AD1804464.316 AD18045 14.933 AD18046 −2.101 AD18047 62.456 AD18048 74.534AD18049 2.284 AD18050 59.621

Example 4 Screening siRNA Sequences for Immunostimulatory Ability

Human PBMC were isolated from freshly collected buffy coats obtainedfrom healthy donors (Research Blood Components, Inc., Boston, Mass.) bya standard Ficoll-Hypaque density centrifugation. Freshly isolated cells(1×10⁵/well) were seeded in 96-well plates and cultured in RPMI 1640GlutaMax medium (Invitrogen) supplemented with 10% heat-inactivatedfetal bovine serum and 1% antibiotic/antimycotic (Invitrogen).

siRNAs were transfected into PBMC using two separate transfectionreagents: GenePorter 2 (GP2; Genlantis) and DOTAP (Roche AppliedScience). The transfection reagent was first diluted in Opti-MEM(Invitrogen) for 5 minutes before mixing with an equal volume ofOpti-MEM containing the siRNA. siRNA/transfection reagent complexes wereincubated as specified by the reagent manufacturers' instructions andsubsequently added to PBMC. siRNAs were used at a final concentration of133 nM. The ratio of RNA to transfection reagent was 33 pmoles and 16.5pmoles, respectively, per ul of GP2 and DOTAP.

Cytokines were detected and quantified in culture supernatants with acommercially available ELISA kit for IFN-α (BMS2161NST) and TNF-α(BMS2231NST); both from Bender MedSystems (Vienna, Austria).

The results are shown in Table 7.

TABLE 7 XBP-1 targeted siRNAs are not immunostimulatory for human PBMCDonor A Donor B pg/ml Transfection IFN-Ξ TNF-Ξ IFN-Ξ TNF-Ξ Medium only−36 ± 5  −20 ± 13 −35 ± 7  125 ± 48 DOTAP only −49 ± 5  −39 ± 4  −36 ±11 110 ± 81 AD-1730  −6 ± 11 1859 ± 276 141 ± 42 1082 ± 181 AD-1955 −35± 8  32 ± 7 −40 ± 10  59 ± 27 AD-2153 302 ± 32  62 ± 46 531 ± 44 158 ±26 AD-5048 473 ± 63 1244 ± 217 592 ± 41  785 ± 121 AD-18028 −39 ± 9  −39± 7  −23 ± 16 162 ± 49 AD-18029 −35 ± 11 −31 ± 8  −26 ± 16  24 ± 40AD-18037 −28 ± 20 −24 ± 14 30 ± 6 −44 ± 27 AD-18038 −24 ± 18  −5 ± 17−37 ± 11  32 ± 56 AD-18040 −31 ± 17 −12 ± 17 −37 ± 8  −43 ± 14

Cytokine Responses of Whole PBMC to Duplex siRNAs Targeting XBP-1

Freshly isolated PBMC from two normal donors (A and B) were transfectedwith test siRNAs using DOTAP and cultured for 24 hours. Subsequently,culture supernatants were collected and IFN-α and TNF-α levels measuredby ELISA. AD-1730, AD-1955, and AD-2153 are sequences that bear no knownhomology to any human genes. AD-1730 and AD-2153 preferentiallystimulate TNF-α and IFN-α, respectively. AD-5048 corresponds to asequence that targets human Apolipoprotein B (Soutschek et al., 2004)and elicits both and IFN-α and TNF-α AD-1995 is a non-stimulatorysequence used as a negative control. The data shown are derived from asingle experiment in which four replicate wells were transfected witheach siRNA or were treated with either DOTAP or medium alone. Valuesrepresent the mean±standard deviation for four biological replicates.

Example 5 The Effect of XBP-1 siRNA on Hepatic Lipogenesis in Mice

Dietary carbohydrates regulate hepatic lipogenesis by controlling theexpression of critical enzymes in glycolysis and lipogenic pathways.XBP-1, a regulator of the Unfolded Protein Response (UPR), is importantfor de novo fatty acid synthesis in the liver, a function unrelated toits role in the UPR. (Lee et al., Science (2009) 320:1492-1496) XBP-1protein expression is induced in the liver by a high carbohydrate dietand controls the induction of genes involved in fatty acid synthesis.Selective deletion of XBP-1 in liver resulted in markedhypocholesterolemia and hypotriglyceridemia secondary to a decreasedproduction of lipids from the liver. (Lee et al. (2009)) Notably, thisphenotype was not accompanied by hepatic steatosis or significantlycompromised protein secretory function.

XBP-1 accelerates de novo fatty acid synthesis in the liver whilepreserving normal hepatic lipid composition, a profile that is highlyrelevant to the treatment of diseases, such as atherosclerosis, that areassociated with dyspipidemia. Inhibition of XBP-1 may also be usefultherapeutics for the treatment of Nonalcoholic Fatty Liver Disease(NAFLD) and steatohepatitis (NASH), which lead to accelerated morbidityand mortality.

In order to determine whether XBP-1 downregulation by siRNAs would be aneffective strategy to reduce lipid levels and treat dyslipidemias andmetabolic syndromes, siRNAs were designed to target XBP-1.

Knock-down of XBP-1 mRNA in the Liver and Decrease of Plasma CholesterolLevels by Lipidoid Formulated siRNA

Animal dosing: Bolus dosing of LNP01 formulated siRNAs in C57/BL6 mice(5/group, 18-20 g body weight, Charles River Laboratories, MA) wasperformed by low volume tail vein injection using a 27G needle. Micewere dosed with two siRNAs targeting XBP-1 (LNP01-18037 and LNP01-18038)and a control luciferase targeting siRNA (LNP01-1955) at 5 and 7.5mg/kg. Animals were kept under an infrared lamp for approximately 3 minprior to dosing to ease injection. 48 hour post dose animals weresacrificed by CO₂-asphyxiation. 0.2 ml blood was collected byretro-orbital bleeding. Liver was harvested and frozen in liquidnitrogen. Serum and livers were stored at −80° C. Total serumcholesterol in mouse serum was measured using the Wako Cholesterol Eenzymatic colorimetric method (Wako Chemicals USA, Inc., Richmond, Va.,USA) according to manufacturer's instructions. Measurements were takenon a VersaMax™ Tunable microplate reader (Molecular Devices, Sunnyvale,Calif.) using SoftMax® Pro software. Message levels of the target geneXBP-1 were measured via bDNA analysis as below.

bDNA analysis: Frozen livers were grinded using 6850 Freezer/MillCryogenic Grinder (SPEX CentriPrep, Inc.) and powders stored at −80° C.until analysis.

XBP-1 mRNA levels were detected using the branched-DNA technology basedQuantiGene® Reagent System (Panomics, Fremont, Calif., U.S.A.) accordingto the protocol. 10-20 mg of frozen liver powders was lysed in 600 ul of0.3 ug/ml Proteinase K (Epicentre®, #MPRK092) in Tissue and Cell LysisSolution (Epicentre®, #MTC096H) at 65° C. for 1 hour. Then 10 ul of thelysates were added to 90 μl of Lysis Working Reagent (1 volume of stockLysis Mixture in two volumes of water) and incubated at 55° C. overnighton Panomics capture plates with probe sets specific to mouse XBP-1 andmouse GAPDH (Panomics, U.S.A.). Capture plates then were processed forsignal amplification and detection according to the protocol andchemiluminescence was read as relative light units (RLUs) on amicroplate luminometer Victor2-Light (Perkin Elmer). The ratio of XBP-1mRNA to GAPDH mRNA in liver lysates was averaged over each treatmentgroup and compared to a control group treated with PBS

As shown in FIG. 6, as compared to the PBS control, treatment of micewith compounds LNP01-18037, and LNP01-18038, but not with unrelatedsiRNA control LNP01-1955 resulted in significant and dose dependent(72-88%) lowering of XBP-1 transcript levels in mouse liver (asindicated by a smaller XBP-1 to GAPDH transcript ratio when normalizedto a PBS control group), indicating that siRNA molecules were active invivo. As shown in FIG. 6, the silencing activity translated in loweringof total cholesterol in those animals.

Example 6 Cleavage of XBP-1 siRNAs

5′RACE was used to examine the cleavage products of XBP-1 siRNAsisolated from livers of mice injected with the oligonucleotides.

Mice were injected with 5 mg/kg or 7.5 mg/kg lipid-formulated XBP-1siRNAs (LNP01-18038, negative control siRNAs targeting luciferase(LNP01-1955), or PBS. Total RNA was isolated from powdered liver samplesusing Trizol (Invitrogen) and RNAeasy mini columns (Qiagen). Twomicrograms of RNA were used for 5′RACE similar to the Generacer kit(Invitrogen) protocol. The oligonucleotide adaptor was ligated directlyto total RNA using T4 RNA ligase (2U) for 1 hour at 37° C. The ligationmixture was reverse transcribed using the XBP-1-specific oligo5′-GGAAGCAGAGAGTGGAGAAAGAAATGCTAAGG-3′ (SEQ ID NO:4335) usingSuperscript™ III (Invitrogen) for 1 hour at 50° C., then 15 min. at 70°C. cDNA was amplified using 3 ul of cDNA amplified with Platinum Taq(Invitrogen) for 35 cycles where Tm=62° C. with oligos5′-CGACTGGAGCACGAGGACACTGACATGG-3′ (SEQ ID NO:4336) and5′-CCAGTGTTATGTGGCTCTTTAGACACTAATCAG-3′ (SEQ ID NO:4337). PCR productswere examined by gel electrophoresis, purified, and cloned intopCR4-TOPO vector for sequencing (Invitrogen).

PCR experiments on the 5′ RACE product were performed in a blindfashion. One round of PCR was performed using Tm=62° C., for 35 cycles.The expected XBP-1 product size was 320 bp. The PCR products wereroughly the correct size in all experimental samples, but productsappeared to exhibit a high level of degradation the same location as thesiRNA-intended cleavage site. Three bands from each of the experimentalgroups were cut from agarose gels for cloning and sequencing.

The control groups yielded clones with several degradation productsresulting from cleavage around but not located at the expected cleavagesite. The expected and observed cleavage products in the negativecontrol samples are shown in FIG. 1A. The AD18038 siRNA was expected tocleave after nucleotide 925 in the XBP-1 transcript (see FIGS. 1A, 1B,and 3). Thus, no cleavage products at nucleotide position 925 wereexpected, and in fact, none were observed, in the negative controlproducts (FIG. 1A). Degradation products in the negative control sampleswere found at positions −49, −35, −32(2), −31, −30(2), −28, −24, −22,−16(2), −17, −15, −14, −12, −11, −9, +8, +13, +65, and +68, relative tothe intended cleavage site of the XBP-1 siRNA AD18038.

The expected siRNA-mediated cleavage product was found in 76.5% of theclones derived from the AD18038-treated groups (FIG. 1B). Degradationproducts were found from cleavage at positions −30, −10, −8, −5, −3, +1,+3, and +14, relative to the intended cleavage site of the XBP-1 siRNAAD 18038.

TABLE 8 XBP-1 human/Rhesus siRNAs Oligo Name/ SEQ SEQ Positions ontarget ID ID sequence (5′ to 3′) sense (5′-3′) NO: antisense (5′-3′) NO:NM_005080_390-408 AGAAAAUCAGCUUUUACGA 1 UCGUAAAAGCUGAUUUUCU 2NM_005080_1184-1202 UCCCCAGCUGAUUAGUGUC 3 GACACUAAUCAGCUGGGGA 4NM_005080_1494-1512 UACUUAUUAUGUAAGGGUC 5 GACCCUUACAUAAUAAGUA 6NM_005080_1463-1481 UAUCUUAAAAGGGUGGUAG 7 CUACCACCCUUUUAAGAUA 8NM_005080_610-628 CCAUGGAUUCUGGCGGUAU 9 AUACCGCCAGAAUCCAUGG 10NM_005080_823-841 UUAAUGAACUAAUUCGUUU 11 AAACGAAUUAGUUCAUUAA 12NM_005080_1507-1525 AGGGUCAUUAGACAAAUGU 13 ACAUUUGUCUAAUGACCCU 14NM_005080_827-845 UGAACUAAUUCGUUUUGAC 15 GUCAAAACGAAUUAGUUCA 16NM_005080_1503-1521 UGUAAGGGUCAUUAGACAA 17 UUGUCUAAUGACCCUUACA 18NM_005080_829-847 AACUAAUUCGUUUUGACCA 19 UGGUCAAAACGAAUUAGUU 20NM_005080_1783-1801 UAUUUAAAACUACCCAUGC 21 GCAUGGGUAGUUUUAAAUA 22NM_005080_1183-1201 UUCCCCAGCUGAUUAGUGU 23 ACACUAAUCAGCUGGGGAA 24NM_005080_1501-1519 UAUGUAAGGGUCAUUAGAC 25 GUCUAAUGACCCUUACAUA 26NM_005080_1504-1522 GUAAGGGUCAUUAGACAAA 27 UUUGUCUAAUGACCCUUAC 28NM_005080_734-752 GCUCCCAGAGGUCUACCCA 29 UGGGUAGACCUCUGGGAGC 30NM_005080_893-911 GAGCCAAGCUAAUGUGGUA 31 UACCACAUUAGCUUGGCUC 32NM_005080_1064-1082 CUGCCUACUGGAUGCUUAC 33 GUAAGCAUCCAGUAGGCAG 34NM_005080_1066-1084 GCCUACUGGAUGCUUACAG 35 CUGUAAGCAUCCAGUAGGC 36NM_005080_1136-1154 GCUUGGUGUAAACCAUUCU 37 AGAAUGGUUUACACCAAGC 38NM_005080_1137-1155 CUUGGUGUAAACCAUUCUU 39 AAGAAUGGUUUACACCAAG 40NM_005080_1182-1200 UUUCCCCAGCUGAUUAGUG 41 CACUAAUCAGCUGGGGAAA 42NM_005080_1186-1204 CCCAGCUGAUUAGUGUCUA 43 UAGACACUAAUCAGCUGGG 44NM_005080_1189-1207 AGCUGAUUAGUGUCUAAGG 45 CCUUAGACACUAAUCAGCU 46NM_005080_1224-1242 UGCCCUUUUCCUUGACUAU 47 AUAGUCAAGGAAAAGGGCA 48NM_005080_1229-1247 UUUUCCUUGACUAUUACAC 49 GUGUAAUAGUCAAGGAAAA 50NM_005080_1235-1253 UUGACUAUUACACUGCCUG 51 CAGGCAGUGUAAUAGUCAA 52NM_005080_1236-1254 UGACUAUUACACUGCCUGG 53 CCAGGCAGUGUAAUAGUCA 54NM_005080_1438-1456 ACUACAGCUUUUAAGAUUG 55 CAAUCUUAAAAGCUGUAGU 56NM_005080_1441-1459 ACAGCUUUUAAGAUUGUAC 57 GUACAAUCUUAAAAGCUGU 58NM_005080_1442-1460 CAGCUUUUAAGAUUGUACU 59 AGUACAAUCUUAAAAGCUG 60NM_005080_1493-1511 AUACUUAUUAUGUAAGGGU 61 ACCCUUACAUAAUAAGUAU 62NM_005080_1502-1520 AUGUAAGGGUCAUUAGACA 63 UGUCUAAUGACCCUUACAU 64NM_005080_1506-1524 AAGGGUCAUUAGACAAAUG 65 CAUUUGUCUAAUGACCCUU 66NM_005080_1594-1612 UUGCCUCCAGUUUUAGGUC 67 GACCUAAAACUGGAGGCAA 68NM_005080_1790-1808 AACUACCCAUGCAAUUAAA 69 UUUAAUUGCAUGGGUAGUU 70NM_005080_304-322 ACUGCCAGAGAUCGAAAGA 71 UCUUUCGAUCUCUGGCAGU 72NM_005080_305-323 CUGCCAGAGAUCGAAAGAA 73 UUCUUUCGAUCUCUGGCAG 74NM_005080_395-413 AUCAGCUUUUACGAGAGAA 75 UUCUCUCGUAAAAGCUGAU 76NM_005080_609-627 CCCAUGGAUUCUGGCGGUA 77 UACCGCCAGAAUCCAUGGG 78NM_005080_611-629 CAUGGAUUCUGGCGGUAUU 79 AAUACCGCCAGAAUCCAUG 80NM_005080_617-635 UUCUGGCGGUAUUGACUCU 81 AGAGUCAAUACCGCCAGAA 82NM_005080_621-639 GGCGGUAUUGACUCUUCAG 83 CUGAAGAGUCAAUACCGCC 84NM_005080_641-659 UUCAGAGUCUGAUAUCCUG 85 CAGGAUAUCAGACUCUGAA 86NM_005080_648-666 UCUGAUAUCCUGUUGGGCA 87 UGCCCAACAGGAUAUCAGA 88NM_005080_651-669 GAUAUCCUGUUGGGCAUUC 89 GAAUGCCCAACAGGAUAUC 90NM_005080_735-753 CUCCCAGAGGUCUACCCAG 91 CUGGGUAGACCUCUGGGAG 92NM_005080_753-771 GAAGGACCCAGUUCCUUAC 93 GUAAGGAACUGGGUCCUUC 94NM_005080_794-812 GGGGACGUCAUCAGCCAAG 95 CUUGGCUGAUGACGUCCCC 96NM_005080_826-844 AUGAACUAAUUCGUUUUGA 97 UCAAAACGAAUUAGUUCAU 98NM_005080_836-854 UCGUUUUGACCACAUAUAU 99 AUAUAUGUGGUCAAAACGA 100NM_005080_840-858 UUUGACCACAUAUAUACCA 101 UGGUAUAUAUGUGGUCAAA 102NM_005080_841-859 UUGACCACAUAUAUACCAA 103 UUGGUAUAUAUGUGGUCAA 104NM_005080_847-865 ACAUAUAUACCAAGCCCCU 105 AGGGGCUUGGUAUAUAUGU 106NM_005080_894-912 AGCCAAGCUAAUGUGGUAG 107 CUACCACAUUAGCUUGGCU 108NM_005080_895-913 GCCAAGCUAAUGUGGUAGU 109 ACUACCACAUUAGCUUGGC 110NM_005080_896-914 CCAAGCUAAUGUGGUAGUG 111 CACUACCACAUUAGCUUGG 112NM_005080_899-917 AGCUAAUGUGGUAGUGAAA 113 UUUCACUACCACAUUAGCU 114NM_005080_908-926 GGUAGUGAAAAUCGAGGAA 115 UUCCUCGAUUUUCACUACC 116NM_005080_917-935 AAUCGAGGAAGCACCUCUC 117 GAGAGGUGCUUCCUCGAUU 118NM_005080_937-955 GCCCCUCAGAGAAUGAUCA 119 UGAUCAUUCUCUGAGGGGC 120NM_005080_950-968 UGAUCACCCUGAAUUCAUU 121 AAUGAAUUCAGGGUGAUCA 122NM_005080_1185-1203 CCCCAGCUGAUUAGUGUCU 123 AGACACUAAUCAGCUGGGG 124NM_005080_1187-1205 CCAGCUGAUUAGUGUCUAA 125 UUAGACACUAAUCAGCUGG 126NM_005080_1153-1171 CUUGGGAGGACACUUUUGC 127 GCAAAAGUGUCCUCCCAAG 128NM_005080_1787-1805 UAAAACUACCCAUGCAAUU 129 AAUUGCAUGGGUAGUUUUA 130NM_005080_606-624 CUCCCCAUGGAUUCUGGCG 131 CGCCAGAAUCCAUGGGGAG 132NM_005080_1019-1037 UAUCUCAAAUCUGCUUUCA 133 UGAAAGCAGAUUUGAGAUA 134NM_005080_1072-1090 UGGAUGCUUACAGUGACUG 135 CAGUCACUGUAAGCAUCCA 136NM_005080_1228-1246 CUUUUCCUUGACUAUUACA 137 UGUAAUAGUCAAGGAAAAG 138NM_005080_1461-1479 UUUAUCUUAAAAGGGUGGU 139 ACCACCCUUUUAAGAUAAA 140NM_005080_1495-1513 ACUUAUUAUGUAAGGGUCA 141 UGACCCUUACAUAAUAAGU 142NM_005080_1496-1514 CUUAUUAUGUAAGGGUCAU 143 AUGACCCUUACAUAAUAAG 144NM_005080_1500-1518 UUAUGUAAGGGUCAUUAGA 145 UCUAAUGACCCUUACAUAA 146NM_005080_1644-1662 CCUGCUGAGGGGGCUCUUU 147 AAAGAGCCCCCUCAGCAGG 148NM_005080_1708-1726 AUAGAAAUUUACUAUGUAA 149 UUACAUAGUAAAUUUCUAU 150NM_005080_302-320 AGACUGCCAGAGAUCGAAA 151 UUUCGAUCUCUGGCAGUCU 152NM_005080_607-625 UCCCCAUGGAUUCUGGCGG 153 CCGCCAGAAUCCAUGGGGA 154NM_005080_824-842 UAAUGAACUAAUUCGUUUU 155 AAAACGAAUUAGUUCAUUA 156NM_005080_953-971 UCACCCUGAAUUCAUUGUC 157 GACAAUGAAUUCAGGGUGA 158NM_005080_1011-1029 GAGCUGGGUAUCUCAAAUC 159 GAUUUGAGAUACCCAGCUC 160NM_005080_1230-1248 UUUCCUUGACUAUUACACU 161 AGUGUAAUAGUCAAGGAAA 162NM_005080_1231-1249 UUCCUUGACUAUUACACUG 163 CAGUGUAAUAGUCAAGGAA 164NM_005080_1290-1308 AAAGCCAAAAUAGAGAGUA 165 UACUCUCUAUUUUGGCUUU 166NM_005080_1331-1349 AUUUGUUCAGAUCUCAUAG 167 CUAUGAGAUCUGAACAAAU 168NM_005080_1460-1478 UUUUAUCUUAAAAGGGUGG 169 CCACCCUUUUAAGAUAAAA 170NM_005080_1670-1688 GUAUACUUCAAGUAAGAUC 171 GAUCUUACUUGAAGUAUAC 172NM_005080_1671-1689 UAUACUUCAAGUAAGAUCA 173 UGAUCUUACUUGAAGUAUA 174NM_005080_1735-1753 UGGAAUUUUUUCCUGCUAG 175 CUAGCAGGAAAAAAUUCCA 176NM_005080_1744-1762 UUCCUGCUAGUGUAGCUUC 177 GAAGCUACACUAGCAGGAA 178NM_005080_1796-1814 CCAUGCAAUUAAAAGGUAC 179 GUACCUUUUAAUUGCAUGG 180NM_005080_343-361 GAACAGCAAGUGGUAGAUU 181 AAUCUACCACUUGCUGUUC 182NM_005080_374-392 ACCAAAAACUUUUGCUAGA 183 UCUAGCAAAAGUUUUUGGU 184NM_005080_375-393 CCAAAAACUUUUGCUAGAA 185 UUCUAGCAAAAGUUUUUGG 186NM_005080_608-626 CCCCAUGGAUUCUGGCGGU 187 ACCGCCAGAAUCCAUGGGG 188NM_005080_652-670 AUAUCCUGUUGGGCAUUCU 189 AGAAUGCCCAACAGGAUAU 190NM_005080_686-704 AGUCAUGUUCUUCAAAUGC 191 GCAUUUGAAGAACAUGACU 192NM_005080_909-927 GUAGUGAAAAUCGAGGAAG 193 CUUCCUCGAUUUUCACUAC 194NM_005080_951-969 GAUCACCCUGAAUUCAUUG 195 CAAUGAAUUCAGGGUGAUC 196NM_005080_952-970 AUCACCCUGAAUUCAUUGU 197 ACAAUGAAUUCAGGGUGAU 198NM_005080_825-843 AAUGAACUAAUUCGUUUUG 199 CAAAACGAAUUAGUUCAUU 200NM_005080_1194-1212 AUUAGUGUCUAAGGAAUGA 201 UCAUUCCUUAGACACUAAU 202NM_005080_831-849 CUAAUUCGUUUUGACCACA 203 UGUGGUCAAAACGAAUUAG 204NM_005080_835-853 UUCGUUUUGACCACAUAUA 205 UAUAUGUGGUCAAAACGAA 206NM_005080_869-887 CUUAGAGAUACCCUCUGAG 207 CUCAGAGGGUAUCUCUAAG 208NM_005080_1246-1264 ACUGCCUGGAGGAUAGCAG 209 CUGCUAUCCUCCAGGCAGU 210NM_005080_1453-1471 AUUGUACUUUUAUCUUAAA 211 UUUAAGAUAAAAGUACAAU 212NM_005080_1512-1530 CAUUAGACAAAUGUCUUGA 213 UCAAGACAUUUGUCUAAUG 214NM_005080_1546-1564 UAUGAAUGGUUCUUUAUCA 215 UGAUAAAGAACCAUUCAUA 216NM_005080_1789-1807 AAACUACCCAUGCAAUUAA 217 UUAAUUGCAUGGGUAGUUU 218NM_005080_325-343 GCUCGAAUGAGUGAGCUGG 219 CCAGCUCACUCAUUCGAGC 220NM_005080_393-411 AAAUCAGCUUUUACGAGAG 221 CUCUCGUAAAAGCUGAUUU 222NM_005080_788-806 GUCAGUGGGGACGUCAUCA 223 UGAUGACGUCCCCACUGAC 224NM_005080_821-839 CAUUAAUGAACUAAUUCGU 225 ACGAAUUAGUUCAUUAAUG 226NM_005080_1514-1532 UUAGACAAAUGUCUUGAAG 227 CUUCAAGACAUUUGUCUAA 228NM_005080_1797-1815 CAUGCAAUUAAAAGGUACA 229 UGUACCUUUUAAUUGCAUG 230NM_005080_833-851 AAUUCGUUUUGACCACAUA 231 UAUGUGGUCAAAACGAAUU 232NM_005080_1509-1527 GGUCAUUAGACAAAUGUCU 233 AGACAUUUGUCUAAUGACC 234NM_005080_1802-1820 AAUUAAAAGGUACAAUGCA 235 UGCAUUGUACCUUUUAAUU 236NM_005080_391-409 GAAAAUCAGCUUUUACGAG 237 CUCGUAAAAGCUGAUUUUC 238NM_005080_843-861 GACCACAUAUAUACCAAGC 239 GCUUGGUAUAUAUGUGGUC 240NM_005080_1508-1526 GGGUCAUUAGACAAAUGUC 241 GACAUUUGUCUAAUGACCC 242NM_005080_1754-1772 UGUAGCUUCUGAAAGGUGC 243 GCACCUUUCAGAAGCUACA 244NM_005080_430-448 GUUGAGAACCAGGAGUUAA 245 UUAACUCCUGGUUCUCAAC 246NM_005080_437-455 ACCAGGAGUUAAGACAGCG 247 CGCUGUCUUAACUCCUGGU 248NM_005080_1465-1483 UCUUAAAAGGGUGGUAGUU 249 AACUACCACCCUUUUAAGA 250NM_005080_1742-1760 UUUUCCUGCUAGUGUAGCU 251 AGCUACACUAGCAGGAAAA 252NM_005080_438-456 CCAGGAGUUAAGACAGCGC 253 GCGCUGUCUUAACUCCUGG 254NM_005080_1060-1078 CUUCCUGCCUACUGGAUGC 255 GCAUCCAGUAGGCAGGAAG 256NM_005080_1067-1085 CCUACUGGAUGCUUACAGU 257 ACUGUAAGCAUCCAGUAGG 258NM_005080_1197-1215 AGUGUCUAAGGAAUGAUCC 259 GGAUCAUUCCUUAGACACU 260NM_005080_1198-1216 GUGUCUAAGGAAUGAUCCA 261 UGGAUCAUUCCUUAGACAC 262NM_005080_1424-1442 UACUAUAAUUGAGAACUAC 263 GUAGUUCUCAAUUAUAGUA 264NM_005080_1464-1482 AUCUUAAAAGGGUGGUAGU 265 ACUACCACCCUUUUAAGAU 266NM_005080_616-634 AUUCUGGCGGUAUUGACUC 267 GAGUCAAUACCGCCAGAAU 268NM_005080_757-775 GACCCAGUUCCUUACCAGC 269 GCUGGUAAGGAACUGGGUC 270NM_005080_785-803 UCUGUCAGUGGGGACGUCA 271 UGACGUCCCCACUGACAGA 272NM_005080_819-837 GCCAUUAAUGAACUAAUUC 273 GAAUUAGUUCAUUAAUGGC 274NM_005080_842-860 UGACCACAUAUAUACCAAG 275 CUUGGUAUAUAUGUGGUCA 276NM_005080_845-863 CCACAUAUAUACCAAGCCC 277 GGGCUUGGUAUAUAUGUGG 278NM_005080_1013-1031 GCUGGGUAUCUCAAAUCUG 279 CAGAUUUGAGAUACCCAGC 280NM_005080_1431-1449 AUUGAGAACUACAGCUUUU 281 AAAAGCUGUAGUUCUCAAU 282NM_005080_1673-1691 UACUUCAAGUAAGAUCAAG 283 CUUGAUCUUACUUGAAGUA 284NM_005080_283-301 AAAAACAGAGUAGCAGCUC 285 GAGCUGCUACUCUGUUUUU 286NM_005080_838-856 GUUUUGACCACAUAUAUAC 287 GUAUAUAUGUGGUCAAAAC 288NM_005080_279-297 ACUGAAAAACAGAGUAGCA 289 UGCUACUCUGUUUUUCAGU 290NM_005080_633-651 UCUUCAGAUUCAGAGUCUG 291 CAGACUCUGAAUCUGAAGA 292NM_005080_1024-1042 CAAAUCUGCUUUCAUCCAG 293 CUGGAUGAAAGCAGAUUUG 294NM_005080_1147-1165 ACCAUUCUUGGGAGGACAC 295 GUGUCCUCCCAAGAAUGGU 296NM_005080_1154-1172 UUGGGAGGACACUUUUGCC 297 GGCAAAAGUGUCCUCCCAA 298NM_005080_1188-1206 CAGCUGAUUAGUGUCUAAG 299 CUUAGACACUAAUCAGCUG 300NM_005080_1192-1210 UGAUUAGUGUCUAAGGAAU 301 AUUCCUUAGACACUAAUCA 302NM_005080_1195-1213 UUAGUGUCUAAGGAAUGAU 303 AUCAUUCCUUAGACACUAA 304NM_005080_1238-1256 ACUAUUACACUGCCUGGAG 305 CUCCAGGCAGUGUAAUAGU 306NM_005080_1548-1566 UGAAUGGUUCUUUAUCAUU 307 AAUGAUAAAGAACCAUUCA 308NM_005080_1549-1567 GAAUGGUUCUUUAUCAUUU 309 AAAUGAUAAAGAACCAUUC 310NM_005080_1677-1695 UCAAGUAAGAUCAAGAAUC 311 GAUUCUUGAUCUUACUUGA 312NM_005080_1707-1725 UAUAGAAAUUUACUAUGUA 313 UACAUAGUAAAUUUCUAUA 314NM_005080_1713-1731 AAUUUACUAUGUAAAUGCU 315 AGCAUUUACAUAGUAAAUU 316NM_005080_1786-1804 UUAAAACUACCCAUGCAAU 317 AUUGCAUGGGUAGUUUUAA 318NM_005080_210-228 GCUGCCCCAGGCGCGCAAG 319 CUUGCGCGCCUGGGGCAGC 320NM_005080_278-296 AACUGAAAAACAGAGUAGC 321 GCUACUCUGUUUUUCAGUU 322NM_005080_284-302 AAAACAGAGUAGCAGCUCA 323 UGAGCUGCUACUCUGUUUU 324NM_005080_290-308 GAGUAGCAGCUCAGACUGC 325 GCAGUCUGAGCUGCUACUC 326NM_005080_342-360 GGAACAGCAAGUGGUAGAU 327 AUCUACCACUUGCUGUUCC 328NM_005080_431-449 UUGAGAACCAGGAGUUAAG 329 CUUAACUCCUGGUUCUCAA 330NM_005080_576-594 GCAGGCCCAGUUGUCACCC 331 GGGUGACAACUGGGCCUGC 332NM_005080_602-620 ACAUCUCCCCAUGGAUUCU 333 AGAAUCCAUGGGGAGAUGU 334NM_005080_618-636 UCUGGCGGUAUUGACUCUU 335 AAGAGUCAAUACCGCCAGA 336NM_005080_678-696 UUGGACCCAGUCAUGUUCU 337 AGAACAUGACUGGGUCCAA 338NM_005080_796-814 GGACGUCAUCAGCCAAGCU 339 AGCUUGGCUGAUGACGUCC 340NM_005080_940-958 CCUCAGAGAAUGAUCACCC 341 GGGUGAUCAUUCUCUGAGG 342NM_005080_954-972 CACCCUGAAUUCAUUGUCU 343 AGACAAUGAAUUCAGGGUG 344NM_005080_977-995 GAAGGAAGAACCUGUAGAA 345 UUCUACAGGUUCUUCCUUC 346NM_005080_1018-1036 GUAUCUCAAAUCUGCUUUC 347 GAAAGCAGAUUUGAGAUAC 348NM_005080_1026-1044 AAUCUGCUUUCAUCCAGCC 349 GGCUGGAUGAAAGCAGAUU 350NM_005080_1138-1156 UUGGUGUAAACCAUUCUUG 351 CAAGAAUGGUUUACACCAA 352NM_005080_1141-1159 GUGUAAACCAUUCUUGGGA 353 UCCCAAGAAUGGUUUACAC 354NM_005080_1142-1160 UGUAAACCAUUCUUGGGAG 355 CUCCCAAGAAUGGUUUACA 356NM_005080_1155-1173 UGGGAGGACACUUUUGCCA 357 UGGCAAAAGUGUCCUCCCA 358NM_005080_1158-1176 GAGGACACUUUUGCCAAUG 359 CAUUGGCAAAAGUGUCCUC 360NM_005080_1193-1211 GAUUAGUGUCUAAGGAAUG 361 CAUUCCUUAGACACUAAUC 362NM_005080_1196-1214 UAGUGUCUAAGGAAUGAUC 363 GAUCAUUCCUUAGACACUA 364NM_005080_1219-1237 ACUGUUGCCCUUUUCCUUG 365 CAAGGAAAAGGGCAACAGU 366NM_005080_107-125 UGUCGGGGCAGCCCGCCUC 367 GAGGCGGGCUGCCCCGACA 368NM_005080_108-126 GUCGGGGCAGCCCGCCUCC 369 GGAGGCGGGCUGCCCCGAC 370NM_005080_1505-1523 UAAGGGUCAUUAGACAAAU 371 AUUUGUCUAAUGACCCUUA 372NM_005080_1567-1585 UCUCUUCCCCCUUUUUGGC 373 GCCAAAAAGGGGGAAGAGA 374NM_005080_1672-1690 AUACUUCAAGUAAGAUCAA 375 UUGAUCUUACUUGAAGUAU 376NM_005080_1678-1696 CAAGUAAGAUCAAGAAUCU 377 AGAUUCUUGAUCUUACUUG 378NM_005080_1778-1796 CCAUUUAUUUAAAACUACC 379 GGUAGUUUUAAAUAAAUGG 380NM_005080_1779-1797 CAUUUAUUUAAAACUACCC 381 GGGUAGUUUUAAAUAAAUG 382NM_005080_280-298 CUGAAAAACAGAGUAGCAG 383 CUGCUACUCUGUUUUUCAG 384NM_005080_282-300 GAAAAACAGAGUAGCAGCU 385 AGCUGCUACUCUGUUUUUC 386NM_005080_288-306 CAGAGUAGCAGCUCAGACU 387 AGUCUGAGCUGCUACUCUG 388NM_005080_291-309 AGUAGCAGCUCAGACUGCC 389 GGCAGUCUGAGCUGCUACU 390NM_005080_347-365 AGCAAGUGGUAGAUUUAGA 391 UCUAAAUCUACCACUUGCU 392NM_005080_397-415 CAGCUUUUACGAGAGAAAA 393 UUUUCUCUCGUAAAAGCUG 394NM_005080_398-416 AGCUUUUACGAGAGAAAAC 395 GUUUUCUCUCGUAAAAGCU 396NM_005080_399-417 GCUUUUACGAGAGAAAACU 397 AGUUUUCUCUCGUAAAAGC 398NM_005080_512-530 UGAGGCCAGUGGCCGGGUC 399 GACCCGGCCACUGGCCUCA 400NM_005080_517-535 CCAGUGGCCGGGUCUGCUG 401 CAGCAGACCCGGCCACUGG 402NM_005080_596-614 UCCAGAACAUCUCCCCAUG 403 CAUGGGGAGAUGUUCUGGA 404NM_005080_598-616 CAGAACAUCUCCCCAUGGA 405 UCCAUGGGGAGAUGUUCUG 406NM_005080_601-619 AACAUCUCCCCAUGGAUUC 407 GAAUCCAUGGGGAGAUGUU 408NM_005080_605-623 UCUCCCCAUGGAUUCUGGC 409 GCCAGAAUCCAUGGGGAGA 410NM_005080_661-679 UGGGCAUUCUGGACAACUU 411 AAGUUGUCCAGAAUGCCCA 412NM_005080_688-706 UCAUGUUCUUCAAAUGCCC 413 GGGCAUUUGAAGAACAUGA 414NM_005080_691-709 UGUUCUUCAAAUGCCCUUC 415 GAAGGGCAUUUGAAGAACA 416NM_005080_828-846 GAACUAAUUCGUUUUGACC 417 GGUCAAAACGAAUUAGUUC 418NM_005080_830-848 ACUAAUUCGUUUUGACCAC 419 GUGGUCAAAACGAAUUAGU 420NM_005080_834-852 AUUCGUUUUGACCACAUAU 421 AUAUGUGGUCAAAACGAAU 422NM_005080_846-864 CACAUAUAUACCAAGCCCC 423 GGGGCUUGGUAUAUAUGUG 424NM_005080_870-888 UUAGAGAUACCCUCUGAGA 425 UCUCAGAGGGUAUCUCUAA 426NM_005080_891-909 GAGAGCCAAGCUAAUGUGG 427 CCACAUUAGCUUGGCUCUC 428NM_005080_900-918 GCUAAUGUGGUAGUGAAAA 429 UUUUCACUACCACAUUAGC 430NM_005080_911-929 AGUGAAAAUCGAGGAAGCA 431 UGCUUCCUCGAUUUUCACU 432NM_005080_912-930 GUGAAAAUCGAGGAAGCAC 433 GUGCUUCCUCGAUUUUCAC 434NM_005080_979-997 AGGAAGAACCUGUAGAAGA 435 UCUUCUACAGGUUCUUCCU 436NM_005080_1366-1384 GUCUUUUGACAUCCAGCAG 437 CUGCUGGAUGUCAAAAGAC 438NM_005080_150-168 GGCCCUGCCGCUCAUGGUG 439 CACCAUGAGCGGCAGGGCC 440NM_005080_1437-1455 AACUACAGCUUUUAAGAUU 441 AAUCUUAAAAGCUGUAGUU 442NM_005080_482-500 AAGAGGAGGCGGAAGCCAA 443 TTGGCTTCCGCCTCCTCTT 444NM_005080_580-598 GCCCAGUUGUCACCCCUCC 445 GGAGGGGUGACAACUGGGC 446NM_005080_613-631 UGGAUUCUGGCGGUAUUGA 447 UCAAUACCGCCAGAAUCCA 448NM_005080_1065-1083 UGCCUACUGGAUGCUUACA 449 UGUAAGCAUCCAGUAGGCA 450NM_005080_614-632 GGAUUCUGGCGGUAUUGAC 451 GUCAAUACCGCCAGAAUCC 452NM_005080_640-658 AUUCAGAGUCUGAUAUCCU 453 AGGAUAUCAGACUCUGAAU 454NM_005080_1014-1032 CUGGGUAUCUCAAAUCUGC 455 GCAGAUUUGAGAUACCCAG 456NM_005080_1015-1033 UGGGUAUCUCAAAUCUGCU 457 AGCAGAUUUGAGAUACCCA 458NM_005080_1146-1164 AACCAUUCUUGGGAGGACA 459 UGUCCUCCCAAGAAUGGUU 460NM_005080_1232-1250 UCCUUGACUAUUACACUGC 461 GCAGUGUAAUAGUCAAGGA 462NM_005080_1234-1252 CUUGACUAUUACACUGCCU 463 AGGCAGUGUAAUAGUCAAG 464NM_005080_1237-1255 GACUAUUACACUGCCUGGA 465 UCCAGGCAGUGUAAUAGUC 466NM_005080_1443-1461 AGCUUUUAAGAUUGUACUU 467 AAGUACAAUCUUAAAAGCU 468NM_005080_1462-1480 UUAUCUUAAAAGGGUGGUA 469 UACCACCCUUUUAAGAUAA 470NM_005080_1510-1528 GUCAUUAGACAAAUGUCUU 471 AAGACAUUUGUCUAAUGAC 472NM_005080_1591-1609 GGCUUGCCUCCAGUUUUAG 473 CUAAAACUGGAGGCAAGCC 474NM_005080_1615-1633 UUAGUUUGCUUCUGUAAGC 475 GCUUACAGAAGCAAACUAA 476NM_005080_1716-1734 UUACUAUGUAAAUGCUUGA 477 UCAAGCAUUUACAUAGUAA 478NM_005080_1718-1736 ACUAUGUAAAUGCUUGAUG 479 CAUCAAGCAUUUACAUAGU 480NM_005080_1725-1743 AAAUGCUUGAUGGAAUUUU 481 AAAAUUCCAUCAAGCAUUU 482NM_005080_1748-1766 UGCUAGUGUAGCUUCUGAA 483 UUCAGAAGCUACACUAGCA 484NM_005080_1780-1798 AUUUAUUUAAAACUACCCA 485 UGGGUAGUUUUAAAUAAAU 486NM_005080_1794-1812 ACCCAUGCAAUUAAAAGGU 487 ACCUUUUAAUUGCAUGGGU 488NM_005080_156-174 GCCGCUCAUGGUGCCAGCC 489 GGCUGGCACCAUGAGCGGC 490NM_005080_299-317 CUCAGACUGCCAGAGAUCG 491 CGAUCUCUGGCAGUCUGAG 492NM_005080_344-362 AACAGCAAGUGGUAGAUUU 493 AAAUCUACCACUUGCUGUU 494NM_005080_371-389 AGAACCAAAAACUUUUGCU 495 AGCAAAAGUUUUUGGUUCU 496NM_005080_373-391 AACCAAAAACUUUUGCUAG 497 CUAGCAAAAGUUUUUGGUU 498NM_005080_524-542 CCGGGUCUGCUGAGUCCGC 499 GCGGACUCAGCAGACCCGG 500NM_005080_525-543 CGGGUCUGCUGAGUCCGCA 501 UGCGGACUCAGCAGACCCG 502NM_005080_612-630 AUGGAUUCUGGCGGUAUUG 503 CAAUACCGCCAGAAUCCAU 504NM_005080_615-633 GAUUCUGGCGGUAUUGACU 505 AGUCAAUACCGCCAGAAUC 506NM_005080_645-663 GAGUCUGAUAUCCUGUUGG 507 CCAACAGGAUAUCAGACUC 508NM_005080_792-810 GUGGGGACGUCAUCAGCCA 509 UGGCUGAUGACGUCCCCAC 510NM_005080_905-923 UGUGGUAGUGAAAAUCGAG 511 CUCGAUUUUCACUACCACA 512NM_005080_976-994 UGAAGGAAGAACCUGUAGA 513 UCUACAGGUUCUUCCUUCA 514NM_005080_1244-1262 ACACUGCCUGGAGGAUAGC 515 GCUAUCCUCCAGGCAGUGU 516NM_005080_1791-1809 ACUACCCAUGCAAUUAAAA 517 UUUUAAUUGCAUGGGUAGU 518NM_005080_755-773 AGGACCCAGUUCCUUACCA 519 UGGUAAGGAACUGGGUCCU 520NM_005080_799-817 CGUCAUCAGCCAAGCUGGA 521 UCCAGCUUGGCUGAUGACG 522NM_005080_832-850 UAAUUCGUUUUGACCACAU 523 AUGUGGUCAAAACGAAUUA 524NM_005080_839-857 UUUUGACCACAUAUAUACC 525 GGUAUAUAUGUGGUCAAAA 526NM_005080_100-118 CUGCUUCUGUCGGGGCAGC 527 GCUGCCCCGACAGAAGCAG 528NM_005080_281-299 UGAAAAACAGAGUAGCAGC 529 GCUGCUACUCUGUUUUUCA 530NM_005080_822-840 AUUAAUGAACUAAUUCGUU 531 AACGAAUUAGUUCAUUAAU 532NM_005080_1152-1170 UCUUGGGAGGACACUUUUG 533 CAAAAGUGUCCUCCCAAGA 534NM_005080_1191-1209 CUGAUUAGUGUCUAAGGAA 535 UUCCUUAGACACUAAUCAG 536NM_005080_1225-1243 GCCCUUUUCCUUGACUAUU 537 AAUAGUCAAGGAAAAGGGC 538NM_005080_1227-1245 CCUUUUCCUUGACUAUUAC 539 GUAAUAGUCAAGGAAAAGG 540NM_005080_1239-1257 CUAUUACACUGCCUGGAGG 541 CCUCCAGGCAGUGUAAUAG 542NM_005080_1430-1448 AAUUGAGAACUACAGCUUU 543 AAAGCUGUAGUUCUCAAUU 544NM_005080_1499-1517 AUUAUGUAAGGGUCAUUAG 545 CUAAUGACCCUUACAUAAU 546NM_005080_1553-1571 GGUUCUUUAUCAUUUCUCU 547 AGAGAAAUGAUAAAGAACC 548NM_005080_1585-1603 CAUCCUGGCUUGCCUCCAG 549 CUGGAGGCAAGCCAGGAUG 550NM_005080_1592-1610 GCUUGCCUCCAGUUUUAGG 551 CCUAAAACUGGAGGCAAGC 552NM_005080_1743-1761 UUUCCUGCUAGUGUAGCUU 553 AAGCUACACUAGCAGGAAA 554NM_005080_154-172 CUGCCGCUCAUGGUGCCAG 555 CUGGCACCAUGAGCGGCAG 556NM_005080_193-211 GAGGCAGCGAGCGGGGGGC 557 GCCCCCCGCTCGCTGCCTC 558NM_005080_199-217 GCGAGCGGGGGGCUGCCCC 559 GGGGCAGCCCCCCGCUCGC 560NM_005080_292-310 GUAGCAGCUCAGACUGCCA 561 UGGCAGUCUGAGCUGCUAC 562NM_005080_341-359 UGGAACAGCAAGUGGUAGA 563 UCUACCACUUGCUGUUCCA 564NM_005080_377-395 AAAAACUUUUGCUAGAAAA 565 UUUUCUAGCAAAAGUUUUU 566NM_005080_519-537 AGUGGCCGGGUCUGCUGAG 567 CUCAGCAGACCCGGCCACU 568NM_005080_522-540 GGCCGGGUCUGCUGAGUCC 569 GGACUCAGCAGACCCGGCC 570NM_005080_577-595 CAGGCCCAGUUGUCACCCC 571 GGGGUGACAACUGGGCCUG 572NM_005080_599-617 AGAACAUCUCCCCAUGGAU 573 AUCCAUGGGGAGAUGUUCU 574NM_005080_754-772 AAGGACCCAGUUCCUUACC 575 GGUAAGGAACUGGGUCCUU 576NM_005080_888-906 ACAGAGAGCCAAGCUAAUG 577 CAUUAGCUUGGCUCUCUGU 578NM_005080_939-957 CCCUCAGAGAAUGAUCACC 579 GGUGAUCAUUCUCUGAGGG 580NM_005080_964-982 UCAUUGUCUCAGUGAAGGA 581 UCCUUCACUGAGACAAUGA 582NM_005080_1012-1030 AGCUGGGUAUCUCAAAUCU 583 AGAUUUGAGAUACCCAGCU 584NM_005080_1016-1034 GGGUAUCUCAAAUCUGCUU 585 AAGCAGAUUUGAGAUACCC 586NM_005080_1020-1038 AUCUCAAAUCUGCUUUCAU 587 AUGAAAGCAGAUUUGAGAU 588NM_005080_1025-1043 AAAUCUGCUUUCAUCCAGC 589 GCUGGAUGAAAGCAGAUUU 590NM_005080_1027-1045 AUCUGCUUUCAUCCAGCCA 591 UGGCUGGAUGAAAGCAGAU 592NM_005080_1028-1046 UCUGCUUUCAUCCAGCCAC 593 GUGGCUGGAUGAAAGCAGA 594NM_005080_1030-1048 UGCUUUCAUCCAGCCACUG 595 CAGUGGCUGGAUGAAAGCA 596NM_005080_1031-1049 GCUUUCAUCCAGCCACUGC 597 GCAGUGGCUGGAUGAAAGC 598NM_005080_1032-1050 CUUUCAUCCAGCCACUGCC 599 GGCAGUGGCUGGAUGAAAG 600NM_005080_1033-1051 UUUCAUCCAGCCACUGCCC 601 GGGCAGUGGCUGGAUGAAA 602NM_005080_1056-1074 CCAUCUUCCUGCCUACUGG 603 CCAGUAGGCAGGAAGAUGG 604NM_005080_1057-1075 CAUCUUCCUGCCUACUGGA 605 UCCAGUAGGCAGGAAGAUG 606NM_005080_1058-1076 AUCUUCCUGCCUACUGGAU 607 AUCCAGUAGGCAGGAAGAU 608NM_005080_1059-1077 UCUUCCUGCCUACUGGAUG 609 CAUCCAGUAGGCAGGAAGA 610NM_005080_1061-1079 UUCCUGCCUACUGGAUGCU 611 AGCAUCCAGUAGGCAGGAA 612NM_005080_1063-1081 CCUGCCUACUGGAUGCUUA 613 UAAGCAUCCAGUAGGCAGG 614NM_005080_1069-1087 UACUGGAUGCUUACAGUGA 615 UCACUGUAAGCAUCCAGUA 616NM_005080_1071-1089 CUGGAUGCUUACAGUGACU 617 AGUCACUGUAAGCAUCCAG 618NM_005080_1073-1091 GGAUGCUUACAGUGACUGU 619 ACAGUCACUGUAAGCAUCC 620NM_005080_1075-1093 AUGCUUACAGUGACUGUGG 621 CCACAGUCACUGUAAGCAU 622NM_005080_1076-1094 UGCUUACAGUGACUGUGGA 623 UCCACAGUCACUGUAAGCA 624NM_005080_1078-1096 CUUACAGUGACUGUGGAUA 625 UAUCCACAGUCACUGUAAG 626NM_005080_1139-1157 UGGUGUAAACCAUUCUUGG 627 CCAAGAAUGGUUUACACCA 628NM_005080_1140-1158 GGUGUAAACCAUUCUUGGG 629 CCCAAGAAUGGUUUACACC 630NM_005080_1143-1161 GUAAACCAUUCUUGGGAGG 631 CCUCCCAAGAAUGGUUUAC 632NM_005080_1144-1162 UAAACCAUUCUUGGGAGGA 633 UCCUCCCAAGAAUGGUUUA 634NM_005080_1145-1163 AAACCAUUCUUGGGAGGAC 635 GUCCUCCCAAGAAUGGUUU 636NM_005080_1148-1166 CCAUUCUUGGGAGGACACU 637 AGUGUCCUCCCAAGAAUGG 638NM_005080_1156-1174 GGGAGGACACUUUUGCCAA 639 UUGGCAAAAGUGUCCUCCC 640NM_005080_1157-1175 GGAGGACACUUUUGCCAAU 641 AUUGGCAAAAGUGUCCUCC 642NM_005080_1159-1177 AGGACACUUUUGCCAAUGA 643 UCAUUGGCAAAAGUGUCCU 644NM_005080_1160-1178 GGACACUUUUGCCAAUGAA 645 UUCAUUGGCAAAAGUGUCC 646NM_005080_1190-1208 GCUGAUUAGUGUCUAAGGA 647 UCCUUAGACACUAAUCAGC 648NM_005080_1218-1236 UACUGUUGCCCUUUUCCUU 649 AAGGAAAAGGGCAACAGUA 650NM_005080_1220-1238 CUGUUGCCCUUUUCCUUGA 651 UCAAGGAAAAGGGCAACAG 652NM_005080_1221-1239 UGUUGCCCUUUUCCUUGAC 653 GUCAAGGAAAAGGGCAACA 654NM_005080_1233-1251 CCUUGACUAUUACACUGCC 655 GGCAGUGUAAUAGUCAAGG 656NM_005080_1240-1258 UAUUACACUGCCUGGAGGA 657 UCCUCCAGGCAGUGUAAUA 658NM_005080_1241-1259 AUUACACUGCCUGGAGGAU 659 AUCCUCCAGGCAGUGUAAU 660NM_005080_1242-1260 UUACACUGCCUGGAGGAUA 661 UAUCCUCCAGGCAGUGUAA 662NM_005080_1243-1261 UACACUGCCUGGAGGAUAG 663 CUAUCCUCCAGGCAGUGUA 664NM_005080_1282-1300 UCAUUCAAAAAGCCAAAAU 665 AUUUUGGCUUUUUGAAUGA 666NM_005080_1287-1305 CAAAAAGCCAAAAUAGAGA 667 UCUCUAUUUUGGCUUUUUG 668NM_005080_1289-1307 AAAAGCCAAAAUAGAGAGU 669 ACUCUCUAUUUUGGCUUUU 670NM_005080_1310-1328 ACAGUCCUAGAGAAUUCCU 671 AGGAAUUCUCUAGGACUGU 672NM_005080_1330-1348 UAUUUGUUCAGAUCUCAUA 673 UAUGAGAUCUGAACAAAUA 674NM_005080_1332-1350 UUUGUUCAGAUCUCAUAGA 675 UCUAUGAGAUCUGAACAAA 676NM_005080_1333-1351 UUGUUCAGAUCUCAUAGAU 677 AUCUAUGAGAUCUGAACAA 678NM_005080_1369-1387 UUUUGACAUCCAGCAGUCC 679 GGACUGCUGGAUGUCAAAA 680NM_005080_1370-1388 UUUGACAUCCAGCAGUCCA 681 UGGACUGCUGGAUGUCAAA 682NM_005080_1371-1389 UUGACAUCCAGCAGUCCAA 683 UUGGACUGCUGGAUGUCAA 684NM_005080_101-119 UGCUUCUGUCGGGGCAGCC 685 GGCUGCCCCGACAGAAGCA 686NM_005080_1418-1436 AAAUAUUACUAUAAUUGAG 687 CUCAAUUAUAGUAAUAUUU 688NM_005080_1419-1437 AAUAUUACUAUAAUUGAGA 689 UCUCAAUUAUAGUAAUAUU 690NM_005080_1422-1440 AUUACUAUAAUUGAGAACU 691 AGUUCUCAAUUAUAGUAAU 692NM_005080_102-120 GCUUCUGUCGGGGCAGCCC 693 GGGCUGCCCCGACAGAAGC 694NM_005080_1423-1441 UUACUAUAAUUGAGAACUA 695 UAGUUCUCAAUUAUAGUAA 696NM_005080_1425-1443 ACUAUAAUUGAGAACUACA 697 UGUAGUUCUCAAUUAUAGU 698NM_005080_1427-1445 UAUAAUUGAGAACUACAGC 699 GCUGUAGUUCUCAAUUAUA 700NM_005080_1428-1446 AUAAUUGAGAACUACAGCU 701 AGCUGUAGUUCUCAAUUAU 702NM_005080_1429-1447 UAAUUGAGAACUACAGCUU 703 AAGCUGUAGUUCUCAAUUA 704NM_005080_1432-1450 UUGAGAACUACAGCUUUUA 705 UAAAAGCUGUAGUUCUCAA 706NM_005080_1433-1451 UGAGAACUACAGCUUUUAA 707 UUAAAAGCUGUAGUUCUCA 708NM_005080_1435-1453 AGAACUACAGCUUUUAAGA 709 UCUUAAAAGCUGUAGUUCU 710NM_005080_1439-1457 CUACAGCUUUUAAGAUUGU 711 ACAAUCUUAAAAGCUGUAG 712NM_005080_104-122 UUCUGUCGGGGCAGCCCGC 713 GCGGGCUGCCCCGACAGAA 714NM_005080_1444-1462 GCUUUUAAGAUUGUACUUU 715 AAAGUACAAUCUUAAAAGC 716NM_005080_1445-1463 CUUUUAAGAUUGUACUUUU 717 AAAAGUACAAUCUUAAAAG 718NM_005080_1446-1464 UUUUAAGAUUGUACUUUUA 719 UAAAAGUACAAUCUUAAAA 720NM_005080_1447-1465 UUUAAGAUUGUACUUUUAU 721 AUAAAAGUACAAUCUUAAA 722NM_005080_1448-1466 UUAAGAUUGUACUUUUAUC 723 GAUAAAAGUACAAUCUUAA 724NM_005080_1451-1469 AGAUUGUACUUUUAUCUUA 725 UAAGAUAAAAGUACAAUCU 726NM_005080_1454-1472 UUGUACUUUUAUCUUAAAA 727 UUUUAAGAUAAAAGUACAA 728NM_005080_1458-1476 ACUUUUAUCUUAAAAGGGU 729 ACCCUUUUAAGAUAAAAGU 730NM_005080_1459-1477 CUUUUAUCUUAAAAGGGUG 731 CACCCUUUUAAGAUAAAAG 732NM_005080_106-124 CUGUCGGGGCAGCCCGCCU 733 AGGCGGGCUGCCCCGACAG 734NM_005080_1466-1484 CUUAAAAGGGUGGUAGUUU 735 AAACUACCACCCUUUUAAG 736NM_005080_1486-1504 CCCUAAAAUACUUAUUAUG 737 CAUAAUAAGUAUUUUAGGG 738NM_005080_1487-1505 CCUAAAAUACUUAUUAUGU 739 ACAUAAUAAGUAUUUUAGG 740NM_005080_1489-1507 UAAAAUACUUAUUAUGUAA 741 UUACAUAAUAAGUAUUUUA 742NM_005080_1490-1508 AAAAUACUUAUUAUGUAAG 743 CUUACAUAAUAAGUAUUUU 744NM_005080_1491-1509 AAAUACUUAUUAUGUAAGG 745 CCUUACAUAAUAAGUAUUU 746NM_005080_109-127 UCGGGGCAGCCCGCCUCCG 747 CGGAGGCGGGCUGCCCCGA 748NM_005080_1497-1515 UUAUUAUGUAAGGGUCAUU 749 AAUGACCCUUACAUAAUAA 750NM_005080_1498-1516 UAUUAUGUAAGGGUCAUUA 751 UAAUGACCCUUACAUAAUA 752NM_005080_110-128 CGGGGCAGCCCGCCUCCGC 753 GCGGAGGCGGGCUGCCCCG 754NM_005080_1511-1529 UCAUUAGACAAAUGUCUUG 755 CAAGACAUUUGUCUAAUGA 756NM_005080_1513-1531 AUUAGACAAAUGUCUUGAA 757 UUCAAGACAUUUGUCUAAU 758NM_005080_1516-1534 AGACAAAUGUCUUGAAGUA 759 UACUUCAAGACAUUUGUCU 760NM_005080_1517-1535 GACAAAUGUCUUGAAGUAG 761 CUACUUCAAGACAUUUGUC 762NM_005080_1518-1536 ACAAAUGUCUUGAAGUAGA 763 UCUACUUCAAGACAUUUGU 764NM_005080_1547-1565 AUGAAUGGUUCUUUAUCAU 765 AUGAUAAAGAACCAUUCAU 766NM_005080_1550-1568 AAUGGUUCUUUAUCAUUUC 767 GAAAUGAUAAAGAACCAUU 768NM_005080_1551-1569 AUGGUUCUUUAUCAUUUCU 769 AGAAAUGAUAAAGAACCAU 770NM_005080_1552-1570 UGGUUCUUUAUCAUUUCUC 771 GAGAAAUGAUAAAGAACCA 772NM_005080_1554-1572 GUUCUUUAUCAUUUCUCUU 773 AAGAGAAAUGAUAAAGAAC 774NM_005080_1559-1577 UUAUCAUUUCUCUUCCCCC 775 GGGGGAAGAGAAAUGAUAA 776NM_005080_1560-1578 UAUCAUUUCUCUUCCCCCU 777 AGGGGGAAGAGAAAUGAUA 778NM_005080_1563-1581 CAUUUCUCUUCCCCCUUUU 779 AAAAGGGGGAAGAGAAAUG 780NM_005080_1565-1583 UUUCUCUUCCCCCUUUUUG 781 CAAAAAGGGGGAAGAGAAA 782NM_005080_1566-1584 UUCUCUUCCCCCUUUUUGG 783 CCAAAAAGGGGGAAGAGAA 784NM_005080_1570-1588 CUUCCCCCUUUUUGGCAUC 785 GAUGCCAAAAAGGGGGAAG 786NM_005080_1573-1591 CCCCCUUUUUGGCAUCCUG 787 CAGGAUGCCAAAAAGGGGG 788NM_005080_1578-1596 UUUUUGGCAUCCUGGCUUG 789 CAAGCCAGGAUGCCAAAAA 790NM_005080_1579-1597 UUUUGGCAUCCUGGCUUGC 791 GCAAGCCAGGAUGCCAAAA 792NM_005080_1580-1598 UUUGGCAUCCUGGCUUGCC 793 GGCAAGCCAGGAUGCCAAA 794NM_005080_1581-1599 UUGGCAUCCUGGCUUGCCU 795 AGGCAAGCCAGGAUGCCAA 796NM_005080_1583-1601 GGCAUCCUGGCUUGCCUCC 797 GGAGGCAAGCCAGGAUGCC 798NM_005080_1584-1602 GCAUCCUGGCUUGCCUCCA 799 UGGAGGCAAGCCAGGAUGC 800NM_005080_1586-1604 AUCCUGGCUUGCCUCCAGU 801 ACUGGAGGCAAGCCAGGAU 802NM_005080_1589-1607 CUGGCUUGCCUCCAGUUUU 803 AAAACUGGAGGCAAGCCAG 804NM_005080_1590-1608 UGGCUUGCCUCCAGUUUUA 805 UAAAACUGGAGGCAAGCCA 806NM_005080_1595-1613 UGCCUCCAGUUUUAGGUCC 807 GGACCUAAAACUGGAGGCA 808NM_005080_1616-1634 UAGUUUGCUUCUGUAAGCA 809 UGCUUACAGAAGCAAACUA 810NM_005080_1617-1635 AGUUUGCUUCUGUAAGCAA 811 UUGCUUACAGAAGCAAACU 812NM_005080_1643-1661 ACCUGCUGAGGGGGCUCUU 813 AAGAGCCCCCUCAGCAGGU 814NM_005080_1645-1663 CUGCUGAGGGGGCUCUUUC 815 GAAAGAGCCCCCUCAGCAG 816NM_005080_1646-1664 UGCUGAGGGGGCUCUUUCC 817 GGAAAGAGCCCCCUCAGCA 818NM_005080_1647-1665 GCUGAGGGGGCUCUUUCCC 819 GGGAAAGAGCCCCCUCAGC 820NM_005080_1648-1666 CUGAGGGGGCUCUUUCCCU 821 AGGGAAAGAGCCCCCUCAG 822NM_005080_1649-1667 UGAGGGGGCUCUUUCCCUC 823 GAGGGAAAGAGCCCCCUCA 824NM_005080_1679-1697 AAGUAAGAUCAAGAAUCUU 825 AAGAUUCUUGAUCUUACUU 826NM_005080_1680-1698 AGUAAGAUCAAGAAUCUUU 827 AAAGAUUCUUGAUCUUACU 828NM_005080_1681-1699 GUAAGAUCAAGAAUCUUUU 829 AAAAGAUUCUUGAUCUUAC 830NM_005080_1682-1700 UAAGAUCAAGAAUCUUUUG 831 CAAAAGAUUCUUGAUCUUA 832NM_005080_1683-1701 AAGAUCAAGAAUCUUUUGU 833 ACAAAAGAUUCUUGAUCUU 834NM_005080_1684-1702 AGAUCAAGAAUCUUUUGUG 835 CACAAAAGAUUCUUGAUCU 836NM_005080_1687-1705 UCAAGAAUCUUUUGUGAAA 837 UUUCACAAAAGAUUCUUGA 838NM_005080_1709-1727 UAGAAAUUUACUAUGUAAA 839 UUUACAUAGUAAAUUUCUA 840NM_005080_1710-1728 AGAAAUUUACUAUGUAAAU 841 AUUUACAUAGUAAAUUUCU 842NM_005080_1711-1729 GAAAUUUACUAUGUAAAUG 843 CAUUUACAUAGUAAAUUUC 844NM_005080_1712-1730 AAAUUUACUAUGUAAAUGC 845 GCAUUUACAUAGUAAAUUU 846NM_005080_1714-1732 AUUUACUAUGUAAAUGCUU 847 AAGCAUUUACAUAGUAAAU 848NM_005080_1715-1733 UUUACUAUGUAAAUGCUUG 849 CAAGCAUUUACAUAGUAAA 850NM_005080_1717-1735 UACUAUGUAAAUGCUUGAU 851 AUCAAGCAUUUACAUAGUA 852NM_005080_1719-1737 CUAUGUAAAUGCUUGAUGG 853 CCAUCAAGCAUUUACAUAG 854NM_005080_1721-1739 AUGUAAAUGCUUGAUGGAA 855 UUCCAUCAAGCAUUUACAU 856NM_005080_1722-1740 UGUAAAUGCUUGAUGGAAU 857 AUUCCAUCAAGCAUUUACA 858NM_005080_1723-1741 GUAAAUGCUUGAUGGAAUU 859 AAUUCCAUCAAGCAUUUAC 860NM_005080_1726-1744 AAUGCUUGAUGGAAUUUUU 861 AAAAAUUCCAUCAAGCAUU 862NM_005080_1727-1745 AUGCUUGAUGGAAUUUUUU 863 AAAAAAUUCCAUCAAGCAU 864NM_005080_1728-1746 UGCUUGAUGGAAUUUUUUC 865 GAAAAAAUUCCAUCAAGCA 866NM_005080_1729-1747 GCUUGAUGGAAUUUUUUCC 867 GGAAAAAAUUCCAUCAAGC 868NM_005080_1736-1754 GGAAUUUUUUCCUGCUAGU 869 ACUAGCAGGAAAAAAUUCC 870NM_005080_1739-1757 AUUUUUUCCUGCUAGUGUA 871 UACACUAGCAGGAAAAAAU 872NM_005080_1746-1764 CCUGCUAGUGUAGCUUCUG 873 CAGAAGCUACACUAGCAGG 874NM_005080_1747-1765 CUGCUAGUGUAGCUUCUGA 875 UCAGAAGCUACACUAGCAG 876NM_005080_1749-1767 GCUAGUGUAGCUUCUGAAA 877 UUUCAGAAGCUACACUAGC 878NM_005080_1750-1768 CUAGUGUAGCUUCUGAAAG 879 CUUUCAGAAGCUACACUAG 880NM_005080_1751-1769 UAGUGUAGCUUCUGAAAGG 881 CCUUUCAGAAGCUACACUA 882NM_005080_1752-1770 AGUGUAGCUUCUGAAAGGU 883 ACCUUUCAGAAGCUACACU 884NM_005080_1753-1771 GUGUAGCUUCUGAAAGGUG 885 CACCUUUCAGAAGCUACAC 886NM_005080_1755-1773 GUAGCUUCUGAAAGGUGCU 887 AGCACCUUUCAGAAGCUAC 888NM_005080_1758-1776 GCUUCUGAAAGGUGCUUUC 889 GAAAGCACCUUUCAGAAGC 890NM_005080_1781-1799 UUUAUUUAAAACUACCCAU 891 AUGGGUAGUUUUAAAUAAA 892NM_005080_1782-1800 UUAUUUAAAACUACCCAUG 893 CAUGGGUAGUUUUAAAUAA 894NM_005080_1784-1802 AUUUAAAACUACCCAUGCA 895 UGCAUGGGUAGUUUUAAAU 896NM_005080_1785-1803 UUUAAAACUACCCAUGCAA 897 UUGCAUGGGUAGUUUUAAA 898NM_005080_1788-1806 AAAACUACCCAUGCAAUUA 899 UAAUUGCAUGGGUAGUUUU 900NM_005080_1792-1810 CUACCCAUGCAAUUAAAAG 901 CUUUUAAUUGCAUGGGUAG 902NM_005080_1793-1811 UACCCAUGCAAUUAAAAGG 903 CCUUUUAAUUGCAUGGGUA 904NM_005080_1795-1813 CCCAUGCAAUUAAAAGGUA 905 UACCUUUUAAUUGCAUGGG 906NM_005080_1798-1816 AUGCAAUUAAAAGGUACAA 907 UUGUACCUUUUAAUUGCAU 908NM_005080_1799-1817 UGCAAUUAAAAGGUACAAU 909 AUUGUACCUUUUAAUUGCA 910NM_005080_1800-1818 GCAAUUAAAAGGUACAAUG 911 CAUUGUACCUUUUAAUUGC 912NM_005080_1801-1819 CAAUUAAAAGGUACAAUGC 913 GCAUUGUACCUUUUAAUUG 914NM_005080_146-164 GCCAGGCCCUGCCGCUCAU 915 AUGAGCGGCAGGGCCUGGC 916NM_005080_147-165 CCAGGCCCUGCCGCUCAUG 917 CAUGAGCGGCAGGGCCUGG 918NM_005080_148-166 CAGGCCCUGCCGCUCAUGG 919 CCAUGAGCGGCAGGGCCUG 920NM_005080_149-167 AGGCCCUGCCGCUCAUGGU 921 ACCAUGAGCGGCAGGGCCU 922NM_005080_155-173 UGCCGCUCAUGGUGCCAGC 923 GCUGGCACCAUGAGCGGCA 924NM_005080_157-175 CCGCUCAUGGUGCCAGCCC 925 GGGCUGGCACCAUGAGCGG 926NM_005080_158-176 CGCUCAUGGUGCCAGCCCA 927 UGGGCUGGCACCAUGAGCG 928NM_005080_159-177 GCUCAUGGUGCCAGCCCAG 929 CUGGGCUGGCACCAUGAGC 930NM_005080_188-206 GCCCGGAGGCAGCGAGCGG 931 CCGCTCGCTGCCTCCGGGC 932NM_005080_189-207 CCCGGAGGCAGCGAGCGGG 933 CCCGCTCGCTGCCTCCGGG 934NM_005080_195-213 GGCAGCGAGCGGGGGGCUG 935 CAGCCCCCCGCUCGCUGCC 936NM_005080_196-214 GCAGCGAGCGGGGGGCUGC 937 GCAGCCCCCCGCUCGCUGC 938NM_005080_197-215 CAGCGAGCGGGGGGCUGCC 939 GGCAGCCCCCCGCUCGCUG 940NM_005080_198-216 AGCGAGCGGGGGGCUGCCC 941 GGGCAGCCCCCCGCUCGCU 942NM_005080_205-223 GGGGGGCUGCCCCAGGCGC 943 GCGCCUGGGGCAGCCCCCC 944NM_005080_206-224 GGGGGCUGCCCCAGGCGCG 945 CGCGCCUGGGGCAGCCCCC 946NM_005080_207-225 GGGGCUGCCCCAGGCGCGC 947 GCGCGCCUGGGGCAGCCCC 948NM_005080_211-229 CUGCCCCAGGCGCGCAAGC 949 GCUUGCGCGCCUGGGGCAG 950NM_005080_250-268 AGCCCCGAGGAGAAGGCGC 951 GCGCCTTCTCCTCGGGGCT 952NM_005080_256-274 GAGGAGAAGGCGCUGAGGA 953 UCCUCAGCGCCUUCUCCUC 954NM_005080_263-281 AGGCGCUGAGGAGGAAACU 955 AGUUUCCUCCUCAGCGCCU 956NM_005080_264-282 GGCGCUGAGGAGGAAACUG 957 CAGUUUCCUCCUCAGCGCC 958NM_005080_285-303 AAACAGAGUAGCAGCUCAG 959 CUGAGCUGCUACUCUGUUU 960NM_005080_286-304 AACAGAGUAGCAGCUCAGA 961 UCUGAGCUGCUACUCUGUU 962NM_005080_287-305 ACAGAGUAGCAGCUCAGAC 963 GUCUGAGCUGCUACUCUGU 964NM_005080_294-312 AGCAGCUCAGACUGCCAGA 965 UCUGGCAGUCUGAGCUGCU 966NM_005080_295-313 GCAGCUCAGACUGCCAGAG 967 CUCUGGCAGUCUGAGCUGC 968NM_005080_296-314 CAGCUCAGACUGCCAGAGA 969 UCUCUGGCAGUCUGAGCUG 970NM_005080_298-316 GCUCAGACUGCCAGAGAUC 971 GAUCUCUGGCAGUCUGAGC 972NM_005080_303-321 GACUGCCAGAGAUCGAAAG 973 CUUUCGAUCUCUGGCAGUC 974NM_005080_332-350 UGAGUGAGCUGGAACAGCA 975 UGCUGUUCCAGCUCACUCA 976NM_005080_339-357 GCUGGAACAGCAAGUGGUA 977 UACCACUUGCUGUUCCAGC 978NM_005080_340-358 CUGGAACAGCAAGUGGUAG 979 CUACCACUUGCUGUUCCAG 980NM_005080_345-363 ACAGCAAGUGGUAGAUUUA 981 UAAAUCUACCACUUGCUGU 982NM_005080_346-364 CAGCAAGUGGUAGAUUUAG 983 CUAAAUCUACCACUUGCUG 984NM_005080_348-366 GCAAGUGGUAGAUUUAGAA 985 UUCUAAAUCUACCACUUGC 986NM_005080_349-367 CAAGUGGUAGAUUUAGAAG 987 CUUCUAAAUCUACCACUUG 988NM_005080_352-370 GUGGUAGAUUUAGAAGAAG 989 CUUCUUCUAAAUCUACCAC 990NM_005080_353-371 UGGUAGAUUUAGAAGAAGA 991 UCUUCUUCUAAAUCUACCA 992NM_005080_354-372 GGUAGAUUUAGAAGAAGAG 993 CUCUUCUUCUAAAUCUACC 994NM_005080_355-373 GUAGAUUUAGAAGAAGAGA 995 UCUCUUCUUCUAAAUCUAC 996NM_005080_361-379 UUAGAAGAAGAGAACCAAA 997 UUUGGUUCUCUUCUUCUAA 998NM_005080_366-384 AGAAGAGAACCAAAAACUU 999 AAGUUUUUGGUUCUCUUCU 1000NM_005080_369-387 AGAGAACCAAAAACUUUUG 1001 CAAAAGUUUUUGGUUCUCU 1002NM_005080_370-388 GAGAACCAAAAACUUUUGC 1003 GCAAAAGUUUUUGGUUCUC 1004NM_005080_372-390 GAACCAAAAACUUUUGCUA 1005 UAGCAAAAGUUUUUGGUUC 1006NM_005080_376-394 CAAAAACUUUUGCUAGAAA 1007 UUUCUAGCAAAAGUUUUUG 1008NM_005080_381-399 ACUUUUGCUAGAAAAUCAG 1009 CUGAUUUUCUAGCAAAAGU 1010NM_005080_384-402 UUUGCUAGAAAAUCAGCUU 1011 AAGCUGAUUUUCUAGCAAA 1012NM_005080_388-406 CUAGAAAAUCAGCUUUUAC 1013 GUAAAAGCUGAUUUUCUAG 1014NM_005080_392-410 AAAAUCAGCUUUUACGAGA 1015 UCUCGUAAAAGCUGAUUUU 1016NM_005080_394-412 AAUCAGCUUUUACGAGAGA 1017 UCUCUCGUAAAAGCUGAUU 1018NM_005080_396-414 UCAGCUUUUACGAGAGAAA 1019 UUUCUCUCGUAAAAGCUGA 1020NM_005080_400-418 CUUUUACGAGAGAAAACUC 1021 GAGUUUUCUCUCGUAAAAG 1022NM_005080_421-439 GGCCUUGUAGUUGAGAACC 1023 GGUUCUCAACUACAAGGCC 1024NM_005080_422-440 GCCUUGUAGUUGAGAACCA 1025 UGGUUCUCAACUACAAGGC 1026NM_005080_423-441 CCUUGUAGUUGAGAACCAG 1027 CUGGUUCUCAACUACAAGG 1028NM_005080_425-443 UUGUAGUUGAGAACCAGGA 1029 UCCUGGUUCUCAACUACAA 1030NM_005080_428-446 UAGUUGAGAACCAGGAGUU 1031 AACUCCUGGUUCUCAACUA 1032NM_005080_429-447 AGUUGAGAACCAGGAGUUA 1033 UAACUCCUGGUUCUCAACU 1034NM_005080_432-450 UGAGAACCAGGAGUUAAGA 1035 UCUUAACUCCUGGUUCUCA 1036NM_005080_433-451 GAGAACCAGGAGUUAAGAC 1037 GUCUUAACUCCUGGUUCUC 1038NM_005080_434-452 AGAACCAGGAGUUAAGACA 1039 UGUCUUAACUCCUGGUUCU 1040NM_005080_435-453 GAACCAGGAGUUAAGACAG 1041 CUGUCUUAACUCCUGGUUC 1042NM_005080_436-454 AACCAGGAGUUAAGACAGC 1043 GCUGUCUUAACUCCUGGUU 1044NM_005080_459-477 GGGGAUGGAUGCCCUGGUU 1045 AACCAGGGCAUCCAUCCCC 1046NM_005080_460-478 GGGAUGGAUGCCCUGGUUG 1047 CAACCAGGGCAUCCAUCCC 1048NM_005080_462-480 GAUGGAUGCCCUGGUUGCU 1049 AGCAACCAGGGCAUCCAUC 1050NM_005080_486-504 GGAGGCGGAAGCCAAGGGG 1051 CCCCTTGGCTTCCGCCTCC 1052NM_005080_510-528 AGUGAGGCCAGUGGCCGGG 1053 CCCGGCCACUGGCCUCACU 1054NM_005080_513-531 GAGGCCAGUGGCCGGGUCU 1055 AGACCCGGCCACUGGCCUC 1056NM_005080_514-532 AGGCCAGUGGCCGGGUCUG 1057 CAGACCCGGCCACUGGCCU 1058NM_005080_515-533 GGCCAGUGGCCGGGUCUGC 1059 GCAGACCCGGCCACUGGCC 1060NM_005080_516-534 GCCAGUGGCCGGGUCUGCU 1061 AGCAGACCCGGCCACUGGC 1062NM_005080_520-538 GUGGCCGGGUCUGCUGAGU 1063 ACUCAGCAGACCCGGCCAC 1064NM_005080_521-539 UGGCCGGGUCUGCUGAGUC 1065 GACUCAGCAGACCCGGCCA 1066NM_005080_523-541 GCCGGGUCUGCUGAGUCCG 1067 CGGACUCAGCAGACCCGGC 1068NM_005080_578-596 AGGCCCAGUUGUCACCCCU 1069 AGGGGUGACAACUGGGCCU 1070NM_005080_581-599 CCCAGUUGUCACCCCUCCA 1071 UGGAGGGGUGACAACUGGG 1072NM_005080_582-600 CCAGUUGUCACCCCUCCAG 1073 CUGGAGGGGUGACAACUGG 1074NM_005080_583-601 CAGUUGUCACCCCUCCAGA 1075 UCUGGAGGGGUGACAACUG 1076NM_005080_584-602 AGUUGUCACCCCUCCAGAA 1077 UUCUGGAGGGGUGACAACU 1078NM_005080_585-603 GUUGUCACCCCUCCAGAAC 1079 GUUCUGGAGGGGUGACAAC 1080NM_005080_586-604 UUGUCACCCCUCCAGAACA 1081 UGUUCUGGAGGGGUGACAA 1082NM_005080_587-605 UGUCACCCCUCCAGAACAU 1083 AUGUUCUGGAGGGGUGACA 1084NM_005080_588-606 GUCACCCCUCCAGAACAUC 1085 GAUGUUCUGGAGGGGUGAC 1086NM_005080_589-607 UCACCCCUCCAGAACAUCU 1087 AGAUGUUCUGGAGGGGUGA 1088NM_005080_590-608 CACCCCUCCAGAACAUCUC 1089 GAGAUGUUCUGGAGGGGUG 1090NM_005080_591-609 ACCCCUCCAGAACAUCUCC 1091 GGAGAUGUUCUGGAGGGGU 1092NM_005080_597-615 CCAGAACAUCUCCCCAUGG 1093 CCAUGGGGAGAUGUUCUGG 1094NM_005080_600-618 GAACAUCUCCCCAUGGAUU 1095 AAUCCAUGGGGAGAUGUUC 1096NM_005080_603-621 CAUCUCCCCAUGGAUUCUG 1097 CAGAAUCCAUGGGGAGAUG 1098NM_005080_619-637 CUGGCGGUAUUGACUCUUC 1099 GAAGAGUCAAUACCGCCAG 1100NM_005080_620-638 UGGCGGUAUUGACUCUUCA 1101 UGAAGAGUCAAUACCGCCA 1102NM_005080_622-640 GCGGUAUUGACUCUUCAGA 1103 UCUGAAGAGUCAAUACCGC 1104NM_005080_623-641 CGGUAUUGACUCUUCAGAU 1105 AUCUGAAGAGUCAAUACCG 1106NM_005080_624-642 GGUAUUGACUCUUCAGAUU 1107 AAUCUGAAGAGUCAAUACC 1108NM_005080_625-643 GUAUUGACUCUUCAGAUUC 1109 GAAUCUGAAGAGUCAAUAC 1110NM_005080_626-644 UAUUGACUCUUCAGAUUCA 1111 UGAAUCUGAAGAGUCAAUA 1112NM_005080_629-647 UGACUCUUCAGAUUCAGAG 1113 CUCUGAAUCUGAAGAGUCA 1114NM_005080_632-650 CUCUUCAGAUUCAGAGUCU 1115 AGACUCUGAAUCUGAAGAG 1116NM_005080_634-652 CUUCAGAUUCAGAGUCUGA 1117 UCAGACUCUGAAUCUGAAG 1118NM_005080_637-655 CAGAUUCAGAGUCUGAUAU 1119 AUAUCAGACUCUGAAUCUG 1120NM_005080_638-656 AGAUUCAGAGUCUGAUAUC 1121 GAUAUCAGACUCUGAAUCU 1122NM_005080_639-657 GAUUCAGAGUCUGAUAUCC 1123 GGAUAUCAGACUCUGAAUC 1124NM_005080_642-660 UCAGAGUCUGAUAUCCUGU 1125 ACAGGAUAUCAGACUCUGA 1126NM_005080_643-661 CAGAGUCUGAUAUCCUGUU 1127 AACAGGAUAUCAGACUCUG 1128NM_005080_644-662 AGAGUCUGAUAUCCUGUUG 1129 CAACAGGAUAUCAGACUCU 1130NM_005080_646-664 AGUCUGAUAUCCUGUUGGG 1131 CCCAACAGGAUAUCAGACU 1132NM_005080_649-667 CUGAUAUCCUGUUGGGCAU 1133 AUGCCCAACAGGAUAUCAG 1134NM_005080_650-668 UGAUAUCCUGUUGGGCAUU 1135 AAUGCCCAACAGGAUAUCA 1136NM_005080_653-671 UAUCCUGUUGGGCAUUCUG 1137 CAGAAUGCCCAACAGGAUA 1138NM_005080_658-676 UGUUGGGCAUUCUGGACAA 1139 UUGUCCAGAAUGCCCAACA 1140NM_005080_659-677 GUUGGGCAUUCUGGACAAC 1141 GUUGUCCAGAAUGCCCAAC 1142NM_005080_660-678 UUGGGCAUUCUGGACAACU 1143 AGUUGUCCAGAAUGCCCAA 1144NM_005080_663-681 GGCAUUCUGGACAACUUGG 1145 CCAAGUUGUCCAGAAUGCC 1146NM_005080_664-682 GCAUUCUGGACAACUUGGA 1147 UCCAAGUUGUCCAGAAUGC 1148NM_005080_668-686 UCUGGACAACUUGGACCCA 1149 UGGGUCCAAGUUGUCCAGA 1150NM_005080_671-689 GGACAACUUGGACCCAGUC 1151 GACUGGGUCCAAGUUGUCC 1152NM_005080_676-694 ACUUGGACCCAGUCAUGUU 1153 AACAUGACUGGGUCCAAGU 1154NM_005080_677-695 CUUGGACCCAGUCAUGUUC 1155 GAACAUGACUGGGUCCAAG 1156NM_005080_679-697 UGGACCCAGUCAUGUUCUU 1157 AAGAACAUGACUGGGUCCA 1158NM_005080_680-698 GGACCCAGUCAUGUUCUUC 1159 GAAGAACAUGACUGGGUCC 1160NM_005080_682-700 ACCCAGUCAUGUUCUUCAA 1161 UUGAAGAACAUGACUGGGU 1162NM_005080_687-705 GUCAUGUUCUUCAAAUGCC 1163 GGCAUUUGAAGAACAUGAC 1164NM_005080_689-707 CAUGUUCUUCAAAUGCCCU 1165 AGGGCAUUUGAAGAACAUG 1166NM_005080_695-713 CUUCAAAUGCCCUUCCCCA 1167 UGGGGAAGGGCAUUUGAAG 1168NM_005080_696-714 UUCAAAUGCCCUUCCCCAG 1169 CUGGGGAAGGGCAUUUGAA 1170NM_005080_698-716 CAAAUGCCCUUCCCCAGAG 1171 CUCUGGGGAAGGGCAUUUG 1172NM_005080_731-749 GGAGCUCCCAGAGGUCUAC 1173 GUAGACCUCUGGGAGCUCC 1174NM_005080_732-750 GAGCUCCCAGAGGUCUACC 1175 GGUAGACCUCUGGGAGCUC 1176NM_005080_733-751 AGCUCCCAGAGGUCUACCC 1177 GGGUAGACCUCUGGGAGCU 1178NM_005080_736-754 UCCCAGAGGUCUACCCAGA 1179 UCUGGGUAGACCUCUGGGA 1180NM_005080_737-755 CCCAGAGGUCUACCCAGAA 1181 UUCUGGGUAGACCUCUGGG 1182NM_005080_738-756 CCAGAGGUCUACCCAGAAG 1183 CUUCUGGGUAGACCUCUGG 1184NM_005080_740-758 AGAGGUCUACCCAGAAGGA 1185 UCCUUCUGGGUAGACCUCU 1186NM_005080_741-759 GAGGUCUACCCAGAAGGAC 1187 GUCCUUCUGGGUAGACCUC 1188NM_005080_742-760 AGGUCUACCCAGAAGGACC 1189 GGUCCUUCUGGGUAGACCU 1190NM_005080_743-761 GGUCUACCCAGAAGGACCC 1191 GGGUCCUUCUGGGUAGACC 1192NM_005080_748-766 ACCCAGAAGGACCCAGUUC 1193 GAACUGGGUCCUUCUGGGU 1194NM_005080_749-767 CCCAGAAGGACCCAGUUCC 1195 GGAACUGGGUCCUUCUGGG 1196NM_005080_750-768 CCAGAAGGACCCAGUUCCU 1197 AGGAACUGGGUCCUUCUGG 1198NM_005080_751-769 CAGAAGGACCCAGUUCCUU 1199 AAGGAACUGGGUCCUUCUG 1200NM_005080_752-770 AGAAGGACCCAGUUCCUUA 1201 UAAGGAACUGGGUCCUUCU 1202NM_005080_756-774 GGACCCAGUUCCUUACCAG 1203 CUGGUAAGGAACUGGGUCC 1204NM_005080_758-776 ACCCAGUUCCUUACCAGCC 1205 GGCUGGUAAGGAACUGGGU 1206NM_005080_759-777 CCCAGUUCCUUACCAGCCU 1207 AGGCUGGUAAGGAACUGGG 1208NM_005080_760-778 CCAGUUCCUUACCAGCCUC 1209 GAGGCUGGUAAGGAACUGG 1210NM_005080_761-779 CAGUUCCUUACCAGCCUCC 1211 GGAGGCUGGUAAGGAACUG 1212NM_005080_762-780 AGUUCCUUACCAGCCUCCC 1213 GGGAGGCUGGUAAGGAACU 1214NM_005080_767-785 CUUACCAGCCUCCCUUUCU 1215 AGAAAGGGAGGCUGGUAAG 1216NM_005080_769-787 UACCAGCCUCCCUUUCUCU 1217 AGAGAAAGGGAGGCUGGUA 1218NM_005080_773-791 AGCCUCCCUUUCUCUGUCA 1219 UGACAGAGAAAGGGAGGCU 1220NM_005080_779-797 CCUUUCUCUGUCAGUGGGG 1221 CCCCACUGACAGAGAAAGG 1222NM_005080_786-804 CUGUCAGUGGGGACGUCAU 1223 AUGACGUCCCCACUGACAG 1224NM_005080_787-805 UGUCAGUGGGGACGUCAUC 1225 GAUGACGUCCCCACUGACA 1226NM_005080_789-807 UCAGUGGGGACGUCAUCAG 1227 CUGAUGACGUCCCCACUGA 1228NM_005080_793-811 UGGGGACGUCAUCAGCCAA 1229 UUGGCUGAUGACGUCCCCA 1230NM_005080_795-813 GGGACGUCAUCAGCCAAGC 1231 GCUUGGCUGAUGACGUCCC 1232NM_005080_797-815 GACGUCAUCAGCCAAGCUG 1233 CAGCUUGGCUGAUGACGUC 1234NM_005080_798-816 ACGUCAUCAGCCAAGCUGG 1235 CCAGCUUGGCUGAUGACGU 1236NM_005080_800-818 GUCAUCAGCCAAGCUGGAA 1237 UUCCAGCUUGGCUGAUGAC 1238NM_005080_804-822 UCAGCCAAGCUGGAAGCCA 1239 UGGCUUCCAGCUUGGCUGA 1240NM_005080_806-824 AGCCAAGCUGGAAGCCAUU 1241 AAUGGCUUCCAGCUUGGCU 1242NM_005080_807-825 GCCAAGCUGGAAGCCAUUA 1243 UAAUGGCUUCCAGCUUGGC 1244NM_005080_808-826 CCAAGCUGGAAGCCAUUAA 1245 UUAAUGGCUUCCAGCUUGG 1246NM_005080_809-827 CAAGCUGGAAGCCAUUAAU 1247 AUUAAUGGCUUCCAGCUUG 1248NM_005080_810-828 AAGCUGGAAGCCAUUAAUG 1249 CAUUAAUGGCUUCCAGCUU 1250NM_005080_811-829 AGCUGGAAGCCAUUAAUGA 1251 UCAUUAAUGGCUUCCAGCU 1252NM_005080_813-831 CUGGAAGCCAUUAAUGAAC 1253 GUUCAUUAAUGGCUUCCAG 1254NM_005080_814-832 UGGAAGCCAUUAAUGAACU 1255 AGUUCAUUAAUGGCUUCCA 1256NM_005080_818-836 AGCCAUUAAUGAACUAAUU 1257 AAUUAGUUCAUUAAUGGCU 1258NM_005080_820-838 CCAUUAAUGAACUAAUUCG 1259 CGAAUUAGUUCAUUAAUGG 1260NM_005080_837-855 CGUUUUGACCACAUAUAUA 1261 UAUAUAUGUGGUCAAAACG 1262NM_005080_844-862 ACCACAUAUAUACCAAGCC 1263 GGCUUGGUAUAUAUGUGGU 1264NM_005080_872-890 AGAGAUACCCUCUGAGACA 1265 UGUCUCAGAGGGUAUCUCU 1266NM_005080_873-891 GAGAUACCCUCUGAGACAG 1267 CUGUCUCAGAGGGUAUCUC 1268NM_005080_874-892 AGAUACCCUCUGAGACAGA 1269 UCUGUCUCAGAGGGUAUCU 1270NM_005080_876-894 AUACCCUCUGAGACAGAGA 1271 UCUCUGUCUCAGAGGGUAU 1272NM_005080_889-907 CAGAGAGCCAAGCUAAUGU 1273 ACAUUAGCUUGGCUCUCUG 1274NM_005080_890-908 AGAGAGCCAAGCUAAUGUG 1275 CACAUUAGCUUGGCUCUCU 1276NM_005080_897-915 CAAGCUAAUGUGGUAGUGA 1277 UCACUACCACAUUAGCUUG 1278NM_005080_898-916 AAGCUAAUGUGGUAGUGAA 1279 UUCACUACCACAUUAGCUU 1280NM_005080_901-919 CUAAUGUGGUAGUGAAAAU 1281 AUUUUCACUACCACAUUAG 1282NM_005080_903-921 AAUGUGGUAGUGAAAAUCG 1283 CGAUUUUCACUACCACAUU 1284NM_005080_904-922 AUGUGGUAGUGAAAAUCGA 1285 UCGAUUUUCACUACCACAU 1286NM_005080_906-924 GUGGUAGUGAAAAUCGAGG 1287 CCUCGAUUUUCACUACCAC 1288NM_005080_907-925 UGGUAGUGAAAAUCGAGGA 1289 UCCUCGAUUUUCACUACCA 1290NM_005080_910-928 UAGUGAAAAUCGAGGAAGC 1291 GCUUCCUCGAUUUUCACUA 1292NM_005080_913-931 UGAAAAUCGAGGAAGCACC 1293 GGUGCUUCCUCGAUUUUCA 1294NM_005080_916-934 AAAUCGAGGAAGCACCUCU 1295 AGAGGUGCUUCCUCGAUUU 1296NM_005080_918-936 AUCGAGGAAGCACCUCUCA 1297 UGAGAGGUGCUUCCUCGAU 1298NM_005080_919-937 UCGAGGAAGCACCUCUCAG 1299 CUGAGAGGUGCUUCCUCGA 1300NM_005080_920-938 CGAGGAAGCACCUCUCAGC 1301 GCUGAGAGGUGCUUCCUCG 1302NM_005080_922-940 AGGAAGCACCUCUCAGCCC 1303 GGGCUGAGAGGUGCUUCCU 1304NM_005080_923-941 GGAAGCACCUCUCAGCCCC 1305 GGGGCUGAGAGGUGCUUCC 1306NM_005080_929-947 ACCUCUCAGCCCCUCAGAG 1307 CUCUGAGGGGCUGAGAGGU 1308NM_005080_930-948 CCUCUCAGCCCCUCAGAGA 1309 UCUCUGAGGGGCUGAGAGG 1310NM_005080_931-949 CUCUCAGCCCCUCAGAGAA 1311 UUCUCUGAGGGGCUGAGAG 1312NM_005080_932-950 UCUCAGCCCCUCAGAGAAU 1313 AUUCUCUGAGGGGCUGAGA 1314NM_005080_933-951 CUCAGCCCCUCAGAGAAUG 1315 CAUUCUCUGAGGGGCUGAG 1316NM_005080_934-952 UCAGCCCCUCAGAGAAUGA 1317 UCAUUCUCUGAGGGGCUGA 1318NM_005080_935-953 CAGCCCCUCAGAGAAUGAU 1319 AUCAUUCUCUGAGGGGCUG 1320NM_005080_936-954 AGCCCCUCAGAGAAUGAUC 1321 GAUCAUUCUCUGAGGGGCU 1322NM_005080_938-956 CCCCUCAGAGAAUGAUCAC 1323 GUGAUCAUUCUCUGAGGGG 1324NM_005080_941-959 CUCAGAGAAUGAUCACCCU 1325 AGGGUGAUCAUUCUCUGAG 1326NM_005080_942-960 UCAGAGAAUGAUCACCCUG 1327 CAGGGUGAUCAUUCUCUGA 1328NM_005080_943-961 CAGAGAAUGAUCACCCUGA 1329 UCAGGGUGAUCAUUCUCUG 1330NM_005080_944-962 AGAGAAUGAUCACCCUGAA 1331 UUCAGGGUGAUCAUUCUCU 1332NM_005080_946-964 AGAAUGAUCACCCUGAAUU 1333 AAUUCAGGGUGAUCAUUCU 1334NM_005080_947-965 GAAUGAUCACCCUGAAUUC 1335 GAAUUCAGGGUGAUCAUUC 1336NM_005080_948-966 AAUGAUCACCCUGAAUUCA 1337 UGAAUUCAGGGUGAUCAUU 1338NM_005080_949-967 AUGAUCACCCUGAAUUCAU 1339 AUGAAUUCAGGGUGAUCAU 1340NM_005080_955-973 ACCCUGAAUUCAUUGUCUC 1341 GAGACAAUGAAUUCAGGGU 1342NM_005080_956-974 CCCUGAAUUCAUUGUCUCA 1343 UGAGACAAUGAAUUCAGGG 1344NM_005080_957-975 CCUGAAUUCAUUGUCUCAG 1345 CUGAGACAAUGAAUUCAGG 1346NM_005080_960-978 GAAUUCAUUGUCUCAGUGA 1347 UCACUGAGACAAUGAAUUC 1348NM_005080_961-979 AAUUCAUUGUCUCAGUGAA 1349 UUCACUGAGACAAUGAAUU 1350NM_005080_965-983 CAUUGUCUCAGUGAAGGAA 1351 UUCCUUCACUGAGACAAUG 1352NM_005080_967-985 UUGUCUCAGUGAAGGAAGA 1353 UCUUCCUUCACUGAGACAA 1354NM_005080_968-986 UGUCUCAGUGAAGGAAGAA 1355 UUCUUCCUUCACUGAGACA 1356NM_005080_971-989 CUCAGUGAAGGAAGAACCU 1357 AGGUUCUUCCUUCACUGAG 1358NM_005080_972-990 UCAGUGAAGGAAGAACCUG 1359 CAGGUUCUUCCUUCACUGA 1360NM_005080_973-991 CAGUGAAGGAAGAACCUGU 1361 ACAGGUUCUUCCUUCACUG 1362NM_005080_980-998 GGAAGAACCUGUAGAAGAU 1363 AUCUUCUACAGGUUCUUCC 1364NM_005080_984-1002 GAACCUGUAGAAGAUGACC 1365 GGUCAUCUUCUACAGGUUC 1366NM_005080_986-1004 ACCUGUAGAAGAUGACCUC 1367 GAGGUCAUCUUCUACAGGU 1368NM_005080_1023-1041 UCAAAUCUGCUUUCAUCCA 1369 UGGAUGAAAGCAGAUUUGA 1370NM_005080_1151-1169 UUCUUGGGAGGACACUUUU 1371 AAAAGUGUCCUCCCAAGAA 1372NM_005080_1367-1385 UCUUUUGACAUCCAGCAGU 1373 ACUGCUGGAUGUCAAAAGA 1374NM_005080_1414-1432 UAAGAAAUAUUACUAUAAU 1375 AUUAUAGUAAUAUUUCUUA 1376NM_005080_1415-1433 AAGAAAUAUUACUAUAAUU 1377 AAUUAUAGUAAUAUUUCUU 1378NM_005080_1674-1692 ACUUCAAGUAAGAUCAAGA 1379 UCUUGAUCUUACUUGAAGU 1380NM_005080_1675-1693 CUUCAAGUAAGAUCAAGAA 1381 UUCUUGAUCUUACUUGAAG 1382NM_005080_330-348 AAUGAGUGAGCUGGAACAG 1383 CUGUUCCAGCUCACUCAUU 1384NM_005080_333-351 GAGUGAGCUGGAACAGCAA 1385 UUGCUGUUCCAGCUCACUC 1386NM_005080_592-610 CCCCUCCAGAACAUCUCCC 1387 GGGAGAUGUUCUGGAGGGG 1388NM_005080_665-683 CAUUCUGGACAACUUGGAC 1389 GUCCAAGUUGUCCAGAAUG 1390NM_005080_815-833 GGAAGCCAUUAAUGAACUA 1391 UAGUUCAUUAAUGGCUUCC 1392NM_005080_1029-1047 CUGCUUUCAUCCAGCCACU 1393 AGUGGCUGGAUGAAAGCAG 1394NM_005080_1077-1095 GCUUACAGUGACUGUGGAU 1395 AUCCACAGUCACUGUAAGC 1396NM_005080_1222-1240 GUUGCCCUUUUCCUUGACU 1397 AGUCAAGGAAAAGGGCAAC 1398NM_005080_1285-1303 UUCAAAAAGCCAAAAUAGA 1399 UCUAUUUUGGCUUUUUGAA 1400NM_005080_1334-1352 UGUUCAGAUCUCAUAGAUG 1401 CAUCUAUGAGAUCUGAACA 1402NM_005080_1335-1353 GUUCAGAUCUCAUAGAUGA 1403 UCAUCUAUGAGAUCUGAAC 1404NM_005080_1436-1454 GAACUACAGCUUUUAAGAU 1405 AUCUUAAAAGCUGUAGUUC 1406NM_005080_1449-1467 UAAGAUUGUACUUUUAUCU 1407 AGAUAAAAGUACAAUCUUA 1408NM_005080_1450-1468 AAGAUUGUACUUUUAUCUU 1409 AAGAUAAAAGUACAAUCUU 1410NM_005080_114-132 GCAGCCCGCCUCCGCCGCC 1411 GGCGGCGGAGGCGGGCUGC 1412NM_005080_1555-1573 UUCUUUAUCAUUUCUCUUC 1413 GAAGAGAAAUGAUAAAGAA 1414NM_005080_1556-1574 UCUUUAUCAUUUCUCUUCC 1415 GGAAGAGAAAUGAUAAAGA 1416NM_005080_1561-1579 AUCAUUUCUCUUCCCCCUU 1417 AAGGGGGAAGAGAAAUGAU 1418NM_005080_1562-1580 UCAUUUCUCUUCCCCCUUU 1419 AAAGGGGGAAGAGAAAUGA 1420NM_005080_1569-1587 UCUUCCCCCUUUUUGGCAU 1421 AUGCCAAAAAGGGGGAAGA 1422NM_005080_1588-1606 CCUGGCUUGCCUCCAGUUU 1423 AAACUGGAGGCAAGCCAGG 1424NM_005080_1640-1658 AACACCUGCUGAGGGGGCU 1425 AGCCCCCUCAGCAGGUGUU 1426NM_005080_1641-1659 ACACCUGCUGAGGGGGCUC 1427 GAGCCCCCUCAGCAGGUGU 1428NM_005080_1642-1660 CACCUGCUGAGGGGGCUCU 1429 AGAGCCCCCUCAGCAGGUG 1430NM_005080_1650-1668 GAGGGGGCUCUUUCCCUCA 1431 UGAGGGAAAGAGCCCCCUC 1432NM_005080_1686-1704 AUCAAGAAUCUUUUGUGAA 1433 UUCACAAAAGAUUCUUGAU 1434NM_005080_1745-1763 UCCUGCUAGUGUAGCUUCU 1435 AGAAGCUACACUAGCAGGA 1436NM_005080_138-156 CCCGGCCGGCCAGGCCCUG 1437 CAGGGCCUGGCCGGCCGGG 1438NM_005080_145-163 GGCCAGGCCCUGCCGCUCA 1439 UGAGCGGCAGGGCCUGGCC 1440NM_005080_190-208 CCGGAGGCAGCGAGCGGGG 1441 CCCCGCTCGCTGCCTCCGG 1442NM_005080_191-209 CGGAGGCAGCGAGCGGGGG 1443 CCCCCGCTCGCTGCCTCCG 1444NM_005080_192-210 GGAGGCAGCGAGCGGGGGG 1445 CCCCCCGCTCGCTGCCTCC 1446NM_005080_259-277 GAGAAGGCGCUGAGGAGGA 1447 UCCUCCUCAGCGCCUUCUC 1448NM_005080_261-279 GAAGGCGCUGAGGAGGAAA 1449 UUUCCUCCUCAGCGCCUUC 1450NM_005080_289-307 AGAGUAGCAGCUCAGACUG 1451 CAGUCUGAGCUGCUACUCU 1452NM_005080_363-381 AGAAGAAGAGAACCAAAAA 1453 TTTTTGGTTCTCTTCTTCT 1454NM_005080_365-383 AAGAAGAGAACCAAAAACU 1455 AGUUUUUGGUUCUCUUCUU 1456NM_005080_385-403 UUGCUAGAAAAUCAGCUUU 1457 AAAGCUGAUUUUCUAGCAA 1458NM_005080_461-479 GGAUGGAUGCCCUGGUUGC 1459 GCAACCAGGGCAUCCAUCC 1460NM_005080_490-508 GCGGAAGCCAAGGGGAAUG 1461 CAUUCCCCUUGGCUUCCGC 1462NM_005080_518-536 CAGUGGCCGGGUCUGCUGA 1463 UCAGCAGACCCGGCCACUG 1464NM_005080_673-691 ACAACUUGGACCCAGUCAU 1465 AUGACUGGGUCCAAGUUGU 1466NM_005080_685-703 CAGUCAUGUUCUUCAAAUG 1467 CAUUUGAAGAACAUGACUG 1468NM_005080_730-748 AGGAGCUCCCAGAGGUCUA 1469 UAGACCUCUGGGAGCUCCU 1470NM_005080_772-790 CAGCCUCCCUUUCUCUGUC 1471 GACAGAGAAAGGGAGGCUG 1472NM_005080_801-819 UCAUCAGCCAAGCUGGAAG 1473 CUUCCAGCUUGGCUGAUGA 1474NM_005080_817-835 AAGCCAUUAAUGAACUAAU 1475 AUUAGUUCAUUAAUGGCUU 1476NM_005080_887-905 GACAGAGAGCCAAGCUAAU 1477 AUUAGCUUGGCUCUCUGUC 1478NM_005080_924-942 GAAGCACCUCUCAGCCCCU 1479 AGGGGCUGAGAGGUGCUUC 1480NM_005080_927-945 GCACCUCUCAGCCCCUCAG 1481 CUGAGGGGCUGAGAGGUGC 1482NM_005080_928-946 CACCUCUCAGCCCCUCAGA 1483 UCUGAGGGGCUGAGAGGUG 1484NM_005080_974-992 AGUGAAGGAAGAACCUGUA 1485 UACAGGUUCUUCCUUCACU 1486NM_005080_985-1003 AACCUGUAGAAGAUGACCU 1487 AGGUCAUCUUCUACAGGUU 1488NM_005080_187-205 AGCCCGGAGGCAGCGAGCG 1489 CGCTCGCTGCCTCCGGGCT 1490NM_005080_672-690 GACAACUUGGACCCAGUCA 1491 UGACUGGGUCCAAGUUGUC 1492NM_005080_771-789 CCAGCCUCCCUUUCUCUGU 1493 ACAGAGAAAGGGAGGCUGG 1494NM_005080_1740-1758 UUUUUUCCUGCUAGUGUAG 1495 CUACACUAGCAGGAAAAAA 1496NM_005080_1741-1759 UUUUUCCUGCUAGUGUAGC 1497 GCUACACUAGCAGGAAAAA 1498NM_005080_662-680 GGGCAUUCUGGACAACUUG 1499 CAAGUUGUCCAGAAUGCCC 1500NM_005080_1070-1088 ACUGGAUGCUUACAGUGAC 1501 GUCACUGUAAGCAUCCAGU 1502NM_005080_631-649 ACUCUUCAGAUUCAGAGUC 1503 GACUCUGAAUCUGAAGAGU 1504NM_005080_647-665 GUCUGAUAUCCUGUUGGGC 1505 GCCCAACAGGAUAUCAGAC 1506NM_005080_791-809 AGUGGGGACGUCAUCAGCC 1507 GGCUGAUGACGUCCCCACU 1508NM_005080_981-999 GAAGAACCUGUAGAAGAUG 1509 CAUCUUCUACAGGUUCUUC 1510NM_005080_1068-1086 CUACUGGAUGCUUACAGUG 1511 CACUGUAAGCAUCCAGUAG 1512NM_005080_1391-1409 GUAUUGAGACAUAUUACUG 1513 CAGUAAUAUGUCUCAAUAC 1514NM_005080_1426-1444 CUAUAAUUGAGAACUACAG 1515 CUGUAGUUCUCAAUUAUAG 1516NM_005080_103-121 CUUCUGUCGGGGCAGCCCG 1517 CGGGCUGCCCCGACAGAAG 1518NM_005080_1457-1475 UACUUUUAUCUUAAAAGGG 1519 CCCUUUUAAGAUAAAAGUA 1520NM_005080_1568-1586 CUCUUCCCCCUUUUUGGCA 1521 UGCCAAAAAGGGGGAAGAG 1522NM_005080_1574-1592 CCCCUUUUUGGCAUCCUGG 1523 CCAGGAUGCCAAAAAGGGG 1524NM_005080_1577-1595 CUUUUUGGCAUCCUGGCUU 1525 AAGCCAGGAUGCCAAAAAG 1526NM_005080_1730-1748 CUUGAUGGAAUUUUUUCCU 1527 AGGAAAAAAUUCCAUCAAG 1528NM_005080_1731-1749 UUGAUGGAAUUUUUUCCUG 1529 CAGGAAAAAAUUCCAUCAA 1530NM_005080_1732-1750 UGAUGGAAUUUUUUCCUGC 1531 GCAGGAAAAAAUUCCAUCA 1532NM_005080_293-311 UAGCAGCUCAGACUGCCAG 1533 CUGGCAGUCUGAGCUGCUA 1534NM_005080_350-368 AAGUGGUAGAUUUAGAAGA 1535 UCUUCUAAAUCUACCACUU 1536NM_005080_351-369 AGUGGUAGAUUUAGAAGAA 1537 UUCUUCUAAAUCUACCACU 1538NM_005080_630-648 GACUCUUCAGAUUCAGAGU 1539 ACUCUGAAUCUGAAGAGUC 1540NM_005080_657-675 CUGUUGGGCAUUCUGGACA 1541 UGUCCAGAAUGCCCAACAG 1542NM_005080_670-688 UGGACAACUUGGACCCAGU 1543 ACUGGGUCCAAGUUGUCCA 1544NM_005080_692-710 GUUCUUCAAAUGCCCUUCC 1545 GGAAGGGCAUUUGAAGAAC 1546NM_005080_778-796 CCCUUUCUCUGUCAGUGGG 1547 CCCACUGACAGAGAAAGGG 1548NM_005080_790-808 CAGUGGGGACGUCAUCAGC 1549 GCUGAUGACGUCCCCACUG 1550NM_005080_970-988 UCUCAGUGAAGGAAGAACC 1551 GGUUCUUCCUUCACUGAGA 1552NM_005080_1162-1180 ACACUUUUGCCAAUGAACU 1553 AGUUCAUUGGCAAAAGUGU 1554NM_005080_1368-1386 CUUUUGACAUCCAGCAGUC 1555 GACUGCUGGAUGUCAAAAG 1556NM_005080_1515-1533 UAGACAAAUGUCUUGAAGU 1557 ACUUCAAGACAUUUGUCUA 1558NM_005080_1541-1559 GAAUUUAUGAAUGGUUCUU 1559 AAGAACCAUUCAUAAAUUC 1560NM_005080_1542-1560 AAUUUAUGAAUGGUUCUUU 1561 AAAGAACCAUUCAUAAAUU 1562NM_005080_1571-1589 UUCCCCCUUUUUGGCAUCC 1563 GGAUGCCAAAAAGGGGGAA 1564NM_005080_151-169 GCCCUGCCGCUCAUGGUGC 1565 GCACCAUGAGCGGCAGGGC 1566NM_005080_160-178 CUCAUGGUGCCAGCCCAGA 1567 UCUGGGCUGGCACCAUGAG 1568NM_005080_326-344 CUCGAAUGAGUGAGCUGGA 1569 UCCAGCUCACUCAUUCGAG 1570NM_005080_327-345 UCGAAUGAGUGAGCUGGAA 1571 UUCCAGCUCACUCAUUCGA 1572NM_005080_331-349 AUGAGUGAGCUGGAACAGC 1573 GCUGUUCCAGCUCACUCAU 1574NM_005080_424-442 CUUGUAGUUGAGAACCAGG 1575 CCUGGUUCUCAACUACAAG 1576NM_005080_483-501 AGAGGAGGCGGAAGCCAAG 1577 CTTGGCTTCCGCCTCCTCT 1578NM_005080_579-597 GGCCCAGUUGUCACCCCUC 1579 GAGGGGUGACAACUGGGCC 1580NM_005080_745-763 UCUACCCAGAAGGACCCAG 1581 CUGGGUCCUUCUGGGUAGA 1582NM_005080_746-764 CUACCCAGAAGGACCCAGU 1583 ACUGGGUCCUUCUGGGUAG 1584NM_005080_812-830 GCUGGAAGCCAUUAAUGAA 1585 UUCAUUAAUGGCUUCCAGC 1586NM_005080_871-889 UAGAGAUACCCUCUGAGAC 1587 GUCUCAGAGGGUAUCUCUA 1588NM_005080_892-910 AGAGCCAAGCUAAUGUGGU 1589 ACCACAUUAGCUUGGCUCU 1590NM_005080_978-996 AAGGAAGAACCUGUAGAAG 1591 CUUCUACAGGUUCUUCCUU 1592NM_005080_982-1000 AAGAACCUGUAGAAGAUGA 1593 UCAUCUUCUACAGGUUCUU 1594NM_005080_257-275 AGGAGAAGGCGCUGAGGAG 1595 CUCCUCAGCGCCUUCUCCU 1596NM_005080_364-382 GAAGAAGAGAACCAAAAAC 1597 GTTTTTGGTTCTCTTCTTC 1598NM_005080_816-834 GAAGCCAUUAAUGAACUAA 1599 UUAGUUCAUUAAUGGCUUC 1600NM_005080_884-902 UGAGACAGAGAGCCAAGCU 1601 AGCUUGGCUCUCUGUCUCA 1602NM_005080_925-943 AAGCACCUCUCAGCCCCUC 1603 GAGGGGCUGAGAGGUGCUU 1604NM_005080_1440-1458 UACAGCUUUUAAGAUUGUA 1605 UACAAUCUUAAAAGCUGUA 1606NM_005080_784-802 CUCUGUCAGUGGGGACGUC 1607 GACGUCCCCACUGACAGAG 1608NM_005080_1593-1611 CUUGCCUCCAGUUUUAGGU 1609 ACCUAAAACUGGAGGCAAG 1610NM_005080_301-319 CAGACUGCCAGAGAUCGAA 1611 UUCGAUCUCUGGCAGUCUG 1612NM_005080_674-692 CAACUUGGACCCAGUCAUG 1613 CAUGACUGGGUCCAAGUUG 1614NM_005080_783-801 UCUCUGUCAGUGGGGACGU 1615 ACGUCCCCACUGACAGAGA 1616NM_005080_921-939 GAGGAAGCACCUCUCAGCC 1617 GGCUGAGAGGUGCUUCCUC 1618NM_005080_1226-1244 CCCUUUUCCUUGACUAUUA 1619 UAAUAGUCAAGGAAAAGGG 1620NM_005080_1283-1301 CAUUCAAAAAGCCAAAAUA 1621 UAUUUUGGCUUUUUGAAUG 1622NM_005080_1416-1434 AGAAAUAUUACUAUAAUUG 1623 CAAUUAUAGUAAUAUUUCU 1624NM_005080_1420-1438 AUAUUACUAUAAUUGAGAA 1625 UUCUCAAUUAUAGUAAUAU 1626NM_005080_1488-1506 CUAAAAUACUUAUUAUGUA 1627 UACAUAAUAAGUAUUUUAG 1628NM_005080_1492-1510 AAUACUUAUUAUGUAAGGG 1629 CCCUUACAUAAUAAGUAUU 1630NM_005080_111-129 GGGGCAGCCCGCCUCCGCC 1631 GGCGGAGGCGGGCUGCCCC 1632NM_005080_1639-1657 GAACACCUGCUGAGGGGGC 1633 GCCCCCUCAGCAGGUGUUC 1634NM_005080_1685-1703 GAUCAAGAAUCUUUUGUGA 1635 UCACAAAAGAUUCUUGAUC 1636NM_005080_1733-1751 GAUGGAAUUUUUUCCUGCU 1637 AGCAGGAAAAAAUUCCAUC 1638NM_005080_1734-1752 AUGGAAUUUUUUCCUGCUA 1639 UAGCAGGAAAAAAUUCCAU 1640NM_005080_1737-1755 GAAUUUUUUCCUGCUAGUG 1641 CACUAGCAGGAAAAAAUUC 1642NM_005080_1756-1774 UAGCUUCUGAAAGGUGCUU 1643 AAGCACCUUUCAGAAGCUA 1644NM_005080_1757-1775 AGCUUCUGAAAGGUGCUUU 1645 AAAGCACCUUUCAGAAGCU 1646NM_005080_152-170 CCCUGCCGCUCAUGGUGCC 1647 GGCACCAUGAGCGGCAGGG 1648NM_005080_153-171 CCUGCCGCUCAUGGUGCCA 1649 UGGCACCAUGAGCGGCAGG 1650NM_005080_163-181 AUGGUGCCAGCCCAGAGAG 1651 CUCUCUGGGCUGGCACCAU 1652NM_005080_167-185 UGCCAGCCCAGAGAGGGGC 1653 GCCCCUCUCUGGGCUGGCA 1654NM_005080_200-218 CGAGCGGGGGGCUGCCCCA 1655 UGGGGCAGCCCCCCGCUCG 1656NM_005080_252-270 CCCCGAGGAGAAGGCGCUG 1657 CAGCGCCUUCUCCUCGGGG 1658NM_005080_255-273 CGAGGAGAAGGCGCUGAGG 1659 CCUCAGCGCCUUCUCCUCG 1660NM_005080_260-278 AGAAGGCGCUGAGGAGGAA 1661 UUCCUCCUCAGCGCCUUCU 1662NM_005080_271-289 AGGAGGAAACUGAAAAACA 1663 UGUUUUUCAGUUUCCUCCU 1664NM_005080_297-315 AGCUCAGACUGCCAGAGAU 1665 AUCUCUGGCAGUCUGAGCU 1666NM_005080_300-318 UCAGACUGCCAGAGAUCGA 1667 UCGAUCUCUGGCAGUCUGA 1668NM_005080_335-353 GUGAGCUGGAACAGCAAGU 1669 ACUUGCUGUUCCAGCUCAC 1670NM_005080_368-386 AAGAGAACCAAAAACUUUU 1671 AAAAGUUUUUGGUUCUCUU 1672NM_005080_378-396 AAAACUUUUGCUAGAAAAU 1673 AUUUUCUAGCAAAAGUUUU 1674NM_005080_379-397 AAACUUUUGCUAGAAAAUC 1675 GAUUUUCUAGCAAAAGUUU 1676NM_005080_380-398 AACUUUUGCUAGAAAAUCA 1677 UGAUUUUCUAGCAAAAGUU 1678NM_005080_389-407 UAGAAAAUCAGCUUUUACG 1679 CGUAAAAGCUGAUUUUCUA 1680NM_005080_426-444 UGUAGUUGAGAACCAGGAG 1681 CUCCUGGUUCUCAACUACA 1682NM_005080_427-445 GUAGUUGAGAACCAGGAGU 1683 ACUCCUGGUUCUCAACUAC 1684NM_005080_485-503 AGGAGGCGGAAGCCAAGGG 1685 CCCTTGGCTTCCGCCTCCT 1686NM_005080_487-505 GAGGCGGAAGCCAAGGGGA 1687 TCCCCTTGGCTTCCGCCTC 1688NM_005080_488-506 AGGCGGAAGCCAAGGGGAA 1689 TTCCCCTTGGCTTCCGCCT 1690NM_005080_511-529 GUGAGGCCAGUGGCCGGGU 1691 ACCCGGCCACUGGCCUCAC 1692NM_005080_526-544 GGGUCUGCUGAGUCCGCAG 1693 CUGCGGACUCAGCAGACCC 1694NM_005080_575-593 UGCAGGCCCAGUUGUCACC 1695 GGUGACAACUGGGCCUGCA 1696NM_005080_593-611 CCCUCCAGAACAUCUCCCC 1697 GGGGAGAUGUUCUGGAGGG 1698NM_005080_595-613 CUCCAGAACAUCUCCCCAU 1699 AUGGGGAGAUGUUCUGGAG 1700NM_005080_654-672 AUCCUGUUGGGCAUUCUGG 1701 CCAGAAUGCCCAACAGGAU 1702NM_005080_675-693 AACUUGGACCCAGUCAUGU 1703 ACAUGACUGGGUCCAAGUU 1704NM_005080_683-701 CCCAGUCAUGUUCUUCAAA 1705 UUUGAAGAACAUGACUGGG 1706NM_005080_684-702 CCAGUCAUGUUCUUCAAAU 1707 AUUUGAAGAACAUGACUGG 1708NM_005080_693-711 UUCUUCAAAUGCCCUUCCC 1709 GGGAAGGGCAUUUGAAGAA 1710NM_005080_694-712 UCUUCAAAUGCCCUUCCCC 1711 GGGGAAGGGCAUUUGAAGA 1712NM_005080_726-744 CUGGAGGAGCUCCCAGAGG 1713 CCUCUGGGAGCUCCUCCAG 1714NM_005080_744-762 GUCUACCCAGAAGGACCCA 1715 UGGGUCCUUCUGGGUAGAC 1716NM_005080_765-783 UCCUUACCAGCCUCCCUUU 1717 AAAGGGAGGCUGGUAAGGA 1718NM_005080_768-786 UUACCAGCCUCCCUUUCUC 1719 GAGAAAGGGAGGCUGGUAA 1720NM_005080_777-795 UCCCUUUCUCUGUCAGUGG 1721 CCACUGACAGAGAAAGGGA 1722NM_005080_802-820 CAUCAGCCAAGCUGGAAGC 1723 GCUUCCAGCUUGGCUGAUG 1724NM_005080_877-895 UACCCUCUGAGACAGAGAG 1725 CUCUCUGUCUCAGAGGGUA 1726NM_005080_878-896 ACCCUCUGAGACAGAGAGC 1727 GCUCUCUGUCUCAGAGGGU 1728NM_005080_885-903 GAGACAGAGAGCCAAGCUA 1729 UAGCUUGGCUCUCUGUCUC 1730NM_005080_886-904 AGACAGAGAGCCAAGCUAA 1731 UUAGCUUGGCUCUCUGUCU 1732NM_005080_966-984 AUUGUCUCAGUGAAGGAAG 1733 CUUCCUUCACUGAGACAAU 1734NM_005080_969-987 GUCUCAGUGAAGGAAGAAC 1735 GUUCUUCCUUCACUGAGAC 1736NM_005080_1245-1263 CACUGCCUGGAGGAUAGCA 1737 UGCUAUCCUCCAGGCAGUG 1738NM_005080_1738-1756 AAUUUUUUCCUGCUAGUGU 1739 ACACUAGCAGGAAAAAAUU 1740NM_005080_194-212 AGGCAGCGAGCGGGGGGCU 1741 AGCCCCCCGCUCGCUGCCU 1742NM_005080_209-227 GGCUGCCCCAGGCGCGCAA 1743 UUGCGCGCCUGGGGCAGCC 1744NM_005080_269-287 UGAGGAGGAAACUGAAAAA 1745 UUUUUCAGUUUCCUCCUCA 1746NM_005080_902-920 UAAUGUGGUAGUGAAAAUC 1747 GAUUUUCACUACCACAUUA 1748NM_005080_50-68 UGGUGGUGGUGGCAGCCGC 1749 GCGGCUGCCACCACCACCA 1750NM_005080_1017-1035 GGUAUCUCAAAUCUGCUUU 1751 AAAGCAGAUUUGAGAUACC 1752NM_005080_1021-1039 UCUCAAAUCUGCUUUCAUC 1753 GAUGAAAGCAGAUUUGAGA 1754NM_005080_1022-1040 CUCAAAUCUGCUUUCAUCC 1755 GGAUGAAAGCAGAUUUGAG 1756NM_005080_1062-1080 UCCUGCCUACUGGAUGCUU 1757 AAGCAUCCAGUAGGCAGGA 1758NM_005080_1074-1092 GAUGCUUACAGUGACUGUG 1759 CACAGUCACUGUAAGCAUC 1760NM_005080_1116-1134 UUCAGUGACAUGUCCUCUC 1761 GAGAGGACAUGUCACUGAA 1762NM_005080_1149-1167 CAUUCUUGGGAGGACACUU 1763 AAGUGUCCUCCCAAGAAUG 1764NM_005080_1150-1168 AUUCUUGGGAGGACACUUU 1765 AAAGUGUCCUCCCAAGAAU 1766NM_005080_1161-1179 GACACUUUUGCCAAUGAAC 1767 GUUCAUUGGCAAAAGUGUC 1768NM_005080_1223-1241 UUGCCCUUUUCCUUGACUA 1769 UAGUCAAGGAAAAGGGCAA 1770NM_005080_1280-1298 CUUCAUUCAAAAAGCCAAA 1771 UUUGGCUUUUUGAAUGAAG 1772NM_005080_1281-1299 UUCAUUCAAAAAGCCAAAA 1773 UUUUGGCUUUUUGAAUGAA 1774NM_005080_1284-1302 AUUCAAAAAGCCAAAAUAG 1775 CUAUUUUGGCUUUUUGAAU 1776NM_005080_1286-1304 UCAAAAAGCCAAAAUAGAG 1777 CUCUAUUUUGGCUUUUUGA 1778NM_005080_1288-1306 AAAAAGCCAAAAUAGAGAG 1779 CUCUCUAUUUUGGCUUUUU 1780NM_005080_1365-1383 UGUCUUUUGACAUCCAGCA 1781 UGCUGGAUGUCAAAAGACA 1782NM_005080_1417-1435 GAAAUAUUACUAUAAUUGA 1783 UCAAUUAUAGUAAUAUUUC 1784NM_005080_1421-1439 UAUUACUAUAAUUGAGAAC 1785 GUUCUCAAUUAUAGUAAUA 1786NM_005080_1434-1452 GAGAACUACAGCUUUUAAG 1787 CUUAAAAGCUGUAGUUCUC 1788NM_005080_1452-1470 GAUUGUACUUUUAUCUUAA 1789 UUAAGAUAAAAGUACAAUC 1790NM_005080_105-123 UCUGUCGGGGCAGCCCGCC 1791 GGCGGGCUGCCCCGACAGA 1792NM_005080_1455-1473 UGUACUUUUAUCUUAAAAG 1793 CUUUUAAGAUAAAAGUACA 1794NM_005080_112-130 GGGCAGCCCGCCUCCGCCG 1795 CGGCGGAGGCGGGCUGCCC 1796NM_005080_113-131 GGCAGCCCGCCUCCGCCGC 1797 GCGGCGGAGGCGGGCUGCC 1798NM_005080_1543-1561 AUUUAUGAAUGGUUCUUUA 1799 UAAAGAACCAUUCAUAAAU 1800NM_005080_1544-1562 UUUAUGAAUGGUUCUUUAU 1801 AUAAAGAACCAUUCAUAAA 1802NM_005080_1557-1575 CUUUAUCAUUUCUCUUCCC 1803 GGGAAGAGAAAUGAUAAAG 1804NM_005080_115-133 CAGCCCGCCUCCGCCGCCG 1805 CGGCGGCGGAGGCGGGCUG 1806NM_005080_1564-1582 AUUUCUCUUCCCCCUUUUU 1807 AAAAAGGGGGAAGAGAAAU 1808NM_005080_1572-1590 UCCCCCUUUUUGGCAUCCU 1809 AGGAUGCCAAAAAGGGGGA 1810NM_005080_1575-1593 CCCUUUUUGGCAUCCUGGC 1811 GCCAGGAUGCCAAAAAGGG 1812NM_005080_1576-1594 CCUUUUUGGCAUCCUGGCU 1813 AGCCAGGAUGCCAAAAAGG 1814NM_005080_117-135 GCCCGCCUCCGCCGCCGGA 1815 UCCGGCGGCGGAGGCGGGC 1816NM_005080_1582-1600 UGGCAUCCUGGCUUGCCUC 1817 GAGGCAAGCCAGGAUGCCA 1818NM_005080_1587-1605 UCCUGGCUUGCCUCCAGUU 1819 AACUGGAGGCAAGCCAGGA 1820NM_005080_118-136 CCCGCCUCCGCCGCCGGAG 1821 CUCCGGCGGCGGAGGCGGG 1822NM_005080_119-137 CCGCCUCCGCCGCCGGAGC 1823 GCUCCGGCGGCGGAGGCGG 1824NM_005080_120-138 CGCCUCCGCCGCCGGAGCC 1825 GGCUCCGGCGGCGGAGGCG 1826NM_005080_124-142 UCCGCCGCCGGAGCCCCGG 1827 CCGGGGCUCCGGCGGCGGA 1828NM_005080_126-144 CGCCGCCGGAGCCCCGGCC 1829 GGCCGGGGCTCCGGCGGCG 1830NM_005080_1676-1694 UUCAAGUAAGAUCAAGAAU 1831 AUUCUUGAUCUUACUUGAA 1832NM_005080_127-145 GCCGCCGGAGCCCCGGCCG 1833 CGGCCGGGGCTCCGGCGGC 1834NM_005080_129-147 CGCCGGAGCCCCGGCCGGC 1835 GCCGGCCGGGGCTCCGGCG 1836NM_005080_130-148 GCCGGAGCCCCGGCCGGCC 1837 GGCCGGCCGGGGCTCCGGC 1838NM_005080_131-149 CCGGAGCCCCGGCCGGCCA 1839 TGGCCGGCCGGGGCTCCGG 1840NM_005080_1720-1738 UAUGUAAAUGCUUGAUGGA 1841 UCCAUCAAGCAUUUACAUA 1842NM_005080_1724-1742 UAAAUGCUUGAUGGAAUUU 1843 AAAUUCCAUCAAGCAUUUA 1844NM_005080_132-150 CGGAGCCCCGGCCGGCCAG 1845 CTGGCCGGCCGGGGCTCCG 1846NM_005080_133-151 GGAGCCCCGGCCGGCCAGG 1847 CCTGGCCGGCCGGGGCTCC 1848NM_005080_134-152 GAGCCCCGGCCGGCCAGGC 1849 GCCTGGCCGGCCGGGGCTC 1850NM_005080_136-154 GCCCCGGCCGGCCAGGCCC 1851 GGGCCTGGCCGGCCGGGGC 1852NM_005080_1777-1795 UCCAUUUAUUUAAAACUAC 1853 GUAGUUUUAAAUAAAUGGA 1854NM_005080_137-155 CCCCGGCCGGCCAGGCCCU 1855 AGGGCCUGGCCGGCCGGGG 1856NM_005080_139-157 CCGGCCGGCCAGGCCCUGC 1857 GCAGGGCCUGGCCGGCCGG 1858NM_005080_140-158 CGGCCGGCCAGGCCCUGCC 1859 GGCAGGGCCUGGCCGGCCG 1860NM_005080_141-159 GGCCGGCCAGGCCCUGCCG 1861 CGGCAGGGCCUGGCCGGCC 1862NM_005080_142-160 GCCGGCCAGGCCCUGCCGC 1863 GCGGCAGGGCCUGGCCGGC 1864NM_005080_143-161 CCGGCCAGGCCCUGCCGCU 1865 AGCGGCAGGGCCUGGCCGG 1866NM_005080_144-162 CGGCCAGGCCCUGCCGCUC 1867 GAGCGGCAGGGCCUGGCCG 1868NM_005080_161-179 UCAUGGUGCCAGCCCAGAG 1869 CUCUGGGCUGGCACCAUGA 1870NM_005080_162-180 CAUGGUGCCAGCCCAGAGA 1871 UCUCUGGGCUGGCACCAUG 1872NM_005080_164-182 UGGUGCCAGCCCAGAGAGG 1873 CCUCUCUGGGCUGGCACCA 1874NM_005080_165-183 GGUGCCAGCCCAGAGAGGG 1875 CCCUCUCUGGGCUGGCACC 1876NM_005080_166-184 GUGCCAGCCCAGAGAGGGG 1877 CCCCUCUCUGGGCUGGCAC 1878NM_005080_201-219 GAGCGGGGGGCUGCCCCAG 1879 CUGGGGCAGCCCCCCGCUC 1880NM_005080_202-220 AGCGGGGGGCUGCCCCAGG 1881 CCUGGGGCAGCCCCCCGCU 1882NM_005080_203-221 GCGGGGGGCUGCCCCAGGC 1883 GCCUGGGGCAGCCCCCCGC 1884NM_005080_204-222 CGGGGGGCUGCCCCAGGCG 1885 CGCCUGGGGCAGCCCCCCG 1886NM_005080_208-226 GGGCUGCCCCAGGCGCGCA 1887 UGCGCGCCUGGGGCAGCCC 1888NM_005080_212-230 UGCCCCAGGCGCGCAAGCG 1889 CGCUUGCGCGCCUGGGGCA 1890NM_005080_248-266 UGAGCCCCGAGGAGAAGGC 1891 GCCUUCUCCUCGGGGCUCA 1892NM_005080_251-269 GCCCCGAGGAGAAGGCGCU 1893 AGCGCCUUCUCCUCGGGGC 1894NM_005080_258-276 GGAGAAGGCGCUGAGGAGG 1895 CCUCCUCAGCGCCUUCUCC 1896NM_005080_262-280 AAGGCGCUGAGGAGGAAAC 1897 GUUUCCUCCUCAGCGCCUU 1898NM_005080_265-283 GCGCUGAGGAGGAAACUGA 1899 UCAGUUUCCUCCUCAGCGC 1900NM_005080_266-284 CGCUGAGGAGGAAACUGAA 1901 UUCAGUUUCCUCCUCAGCG 1902NM_005080_267-285 GCUGAGGAGGAAACUGAAA 1903 UUUCAGUUUCCUCCUCAGC 1904NM_005080_268-286 CUGAGGAGGAAACUGAAAA 1905 UUUUCAGUUUCCUCCUCAG 1906NM_005080_270-288 GAGGAGGAAACUGAAAAAC 1907 GUUUUUCAGUUUCCUCCUC 1908NM_005080_272-290 GGAGGAAACUGAAAAACAG 1909 CUGUUUUUCAGUUUCCUCC 1910NM_005080_273-291 GAGGAAACUGAAAAACAGA 1911 UCUGUUUUUCAGUUUCCUC 1912NM_005080_277-295 AAACUGAAAAACAGAGUAG 1913 CUACUCUGUUUUUCAGUUU 1914NM_005080_328-346 CGAAUGAGUGAGCUGGAAC 1915 GUUCCAGCUCACUCAUUCG 1916NM_005080_329-347 GAAUGAGUGAGCUGGAACA 1917 UGUUCCAGCUCACUCAUUC 1918NM_005080_334-352 AGUGAGCUGGAACAGCAAG 1919 CUUGCUGUUCCAGCUCACU 1920NM_005080_336-354 UGAGCUGGAACAGCAAGUG 1921 CACUUGCUGUUCCAGCUCA 1922NM_005080_337-355 GAGCUGGAACAGCAAGUGG 1923 CCACUUGCUGUUCCAGCUC 1924NM_005080_338-356 AGCUGGAACAGCAAGUGGU 1925 ACCACUUGCUGUUCCAGCU 1926NM_005080_356-374 UAGAUUUAGAAGAAGAGAA 1927 UUCUCUUCUUCUAAAUCUA 1928NM_005080_357-375 AGAUUUAGAAGAAGAGAAC 1929 GUUCUCUUCUUCUAAAUCU 1930NM_005080_359-377 AUUUAGAAGAAGAGAACCA 1931 UGGUUCUCUUCUUCUAAAU 1932NM_005080_360-378 UUUAGAAGAAGAGAACCAA 1933 UUGGUUCUCUUCUUCUAAA 1934NM_005080_362-380 UAGAAGAAGAGAACCAAAA 1935 UUUUGGUUCUCUUCUUCUA 1936NM_005080_367-385 GAAGAGAACCAAAAACUUU 1937 AAAGUUUUUGGUUCUCUUC 1938NM_005080_382-400 CUUUUGCUAGAAAAUCAGC 1939 GCUGAUUUUCUAGCAAAAG 1940NM_005080_386-404 UGCUAGAAAAUCAGCUUUU 1941 AAAAGCUGAUUUUCUAGCA 1942NM_005080_401-419 UUUUACGAGAGAAAACUCA 1943 UGAGUUUUCUCUCGUAAAA 1944NM_005080_458-476 UGGGGAUGGAUGCCCUGGU 1945 ACCAGGGCAUCCAUCCCCA 1946NM_005080_484-502 GAGGAGGCGGAAGCCAAGG 1947 CCTTGGCTTCCGCCTCCTC 1948NM_005080_489-507 GGCGGAAGCCAAGGGGAAU 1949 AUUCCCCUUGGCUUCCGCC 1950NM_005080_574-592 GUGCAGGCCCAGUUGUCAC 1951 GUGACAACUGGGCCUGCAC 1952NM_005080_594-612 CCUCCAGAACAUCUCCCCA 1953 UGGGGAGAUGUUCUGGAGG 1954NM_005080_604-622 AUCUCCCCAUGGAUUCUGG 1955 CCAGAAUCCAUGGGGAGAU 1956NM_005080_627-645 AUUGACUCUUCAGAUUCAG 1957 CUGAAUCUGAAGAGUCAAU 1958NM_005080_635-653 UUCAGAUUCAGAGUCUGAU 1959 AUCAGACUCUGAAUCUGAA 1960NM_005080_636-654 UCAGAUUCAGAGUCUGAUA 1961 UAUCAGACUCUGAAUCUGA 1962NM_005080_666-684 AUUCUGGACAACUUGGACC 1963 GGUCCAAGUUGUCCAGAAU 1964NM_005080_667-685 UUCUGGACAACUUGGACCC 1965 GGGUCCAAGUUGUCCAGAA 1966NM_005080_669-687 CUGGACAACUUGGACCCAG 1967 CUGGGUCCAAGUUGUCCAG 1968NM_005080_681-699 GACCCAGUCAUGUUCUUCA 1969 UGAAGAACAUGACUGGGUC 1970NM_005080_690-708 AUGUUCUUCAAAUGCCCUU 1971 AAGGGCAUUUGAAGAACAU 1972NM_005080_718-736 CUGCCAGCCUGGAGGAGCU 1973 AGCUCCUCCAGGCUGGCAG 1974NM_005080_722-740 CAGCCUGGAGGAGCUCCCA 1975 UGGGAGCUCCUCCAGGCUG 1976NM_005080_723-741 AGCCUGGAGGAGCUCCCAG 1977 CUGGGAGCUCCUCCAGGCU 1978NM_005080_724-742 GCCUGGAGGAGCUCCCAGA 1979 UCUGGGAGCUCCUCCAGGC 1980NM_005080_725-743 CCUGGAGGAGCUCCCAGAG 1981 CUCUGGGAGCUCCUCCAGG 1982NM_005080_727-745 UGGAGGAGCUCCCAGAGGU 1983 ACCUCUGGGAGCUCCUCCA 1984NM_005080_728-746 GGAGGAGCUCCCAGAGGUC 1985 GACCUCUGGGAGCUCCUCC 1986NM_005080_739-757 CAGAGGUCUACCCAGAAGG 1987 CCUUCUGGGUAGACCUCUG 1988NM_005080_747-765 UACCCAGAAGGACCCAGUU 1989 AACUGGGUCCUUCUGGGUA 1990NM_005080_763-781 GUUCCUUACCAGCCUCCCU 1991 AGGGAGGCUGGUAAGGAAC 1992NM_005080_764-782 UUCCUUACCAGCCUCCCUU 1993 AAGGGAGGCUGGUAAGGAA 1994NM_005080_766-784 CCUUACCAGCCUCCCUUUC 1995 GAAAGGGAGGCUGGUAAGG 1996NM_005080_770-788 ACCAGCCUCCCUUUCUCUG 1997 CAGAGAAAGGGAGGCUGGU 1998NM_005080_774-792 GCCUCCCUUUCUCUGUCAG 1999 CUGACAGAGAAAGGGAGGC 2000NM_005080_780-798 CUUUCUCUGUCAGUGGGGA 2001 UCCCCACUGACAGAGAAAG 2002NM_005080_781-799 UUUCUCUGUCAGUGGGGAC 2003 GUCCCCACUGACAGAGAAA 2004NM_005080_805-823 CAGCCAAGCUGGAAGCCAU 2005 AUGGCUUCCAGCUUGGCUG 2006NM_005080_44-62 GAGCUAUGGUGGUGGUGGC 2007 GCCACCACCACCAUAGCUC 2008NM_005080_45-63 AGCUAUGGUGGUGGUGGCA 2009 UGCCACCACCACCAUAGCU 2010NM_005080_868-886 UCUUAGAGAUACCCUCUGA 2011 UCAGAGGGUAUCUCUAAGA 2012NM_005080_875-893 GAUACCCUCUGAGACAGAG 2013 CUCUGUCUCAGAGGGUAUC 2014NM_005080_47-65 CUAUGGUGGUGGUGGCAGC 2015 GCUGCCACCACCACCAUAG 2016NM_005080_879-897 CCCUCUGAGACAGAGAGCC 2017 GGCUCUCUGUCUCAGAGGG 2018NM_005080_880-898 CCUCUGAGACAGAGAGCCA 2019 UGGCUCUCUGUCUCAGAGG 2020NM_005080_881-899 CUCUGAGACAGAGAGCCAA 2021 UUGGCUCUCUGUCUCAGAG 2022NM_005080_882-900 UCUGAGACAGAGAGCCAAG 2023 CUUGGCUCUCUGUCUCAGA 2024NM_005080_883-901 CUGAGACAGAGAGCCAAGC 2025 GCUUGGCUCUCUGUCUCAG 2026NM_005080_49-67 AUGGUGGUGGUGGCAGCCG 2027 CGGCUGCCACCACCACCAU 2028NM_005080_914-932 GAAAAUCGAGGAAGCACCU 2029 AGGUGCUUCCUCGAUUUUC 2030NM_005080_915-933 AAAAUCGAGGAAGCACCUC 2031 GAGGUGCUUCCUCGAUUUU 2032NM_005080_926-944 AGCACCUCUCAGCCCCUCA 2033 UGAGGGGCUGAGAGGUGCU 2034NM_005080_945-963 GAGAAUGAUCACCCUGAAU 2035 AUUCAGGGUGAUCAUUCUC 2036NM_005080_958-976 CUGAAUUCAUUGUCUCAGU 2037 ACUGAGACAAUGAAUUCAG 2038NM_005080_959-977 UGAAUUCAUUGUCUCAGUG 2039 CACUGAGACAAUGAAUUCA 2040NM_005080_962-980 AUUCAUUGUCUCAGUGAAG 2041 CUUCACUGAGACAAUGAAU 2042NM_005080_975-993 GUGAAGGAAGAACCUGUAG 2043 CUACAGGUUCUUCCUUCAC 2044NM_005080_983-1001 AGAACCUGUAGAAGAUGAC 2045 GUCAUCUUCUACAGGUUCU 2046NM_005080_128-146 CCGCCGGAGCCCCGGCCGG 2047 CCGGCCGGGGCTCCGGCGG 2048NM_005080_249-267 GAGCCCCGAGGAGAAGGCG 2049 CGCCTTCTCCTCGGGGCTC 2050NM_005080_697-715 UCAAAUGCCCUUCCCCAGA 2051 UCUGGGGAAGGGCAUUUGA 2052NM_005080_729-747 GAGGAGCUCCCAGAGGUCU 2053 AGACCUCUGGGAGCUCCUC 2054NM_005080_776-794 CUCCCUUUCUCUGUCAGUG 2055 CACUGACAGAGAAAGGGAG 2056NM_005080_803-821 AUCAGCCAAGCUGGAAGCC 2057 GGCUUCCAGCUUGGCUGAU 2058NM_005080_254-272 CCGAGGAGAAGGCGCUGAG 2059 CUCAGCGCCUUCUCCUCGG 2060NM_005080_383-401 UUUUGCUAGAAAAUCAGCU 2061 AGCUGAUUUUCUAGCAAAA 2062NM_005080_116-134 AGCCCGCCUCCGCCGCCGG 2063 CCGGCGGCGGAGGCGGGCU 2064NM_005080_123-141 CUCCGCCGCCGGAGCCCCG 2065 CGGGGCUCCGGCGGCGGAG 2066NM_005080_125-143 CCGCCGCCGGAGCCCCGGC 2067 GCCGGGGCTCCGGCGGCGG 2068NM_005080_135-153 AGCCCCGGCCGGCCAGGCC 2069 GGCCTGGCCGGCCGGGGCT 2070NM_005080_253-271 CCCGAGGAGAAGGCGCUGA 2071 UCAGCGCCUUCUCCUCGGG 2072NM_005080_274-292 AGGAAACUGAAAAACAGAG 2073 CUCUGUUUUUCAGUUUCCU 2074NM_005080_655-673 UCCUGUUGGGCAUUCUGGA 2075 UCCAGAAUGCCCAACAGGA 2076NM_005080_775-793 CCUCCCUUUCUCUGUCAGU 2077 ACUGACAGAGAAAGGGAGG 2078NM_005080_46-64 GCUAUGGUGGUGGUGGCAG 2079 CUGCCACCACCACCAUAGC 2080NM_005080_1456-1474 GUACUUUUAUCUUAAAAGG 2081 CCUUUUAAGAUAAAAGUAC 2082NM_005080_1545-1563 UUAUGAAUGGUUCUUUAUC 2083 GAUAAAGAACCAUUCAUAA 2084NM_005080_1558-1576 UUUAUCAUUUCUCUUCCCC 2085 GGGGAAGAGAAAUGAUAAA 2086NM_005080_121-139 GCCUCCGCCGCCGGAGCCC 2087 GGGCUCCGGCGGCGGAGGC 2088NM_005080_122-140 CCUCCGCCGCCGGAGCCCC 2089 GGGGCUCCGGCGGCGGAGG 2090NM_005080_247-265 CUGAGCCCCGAGGAGAAGG 2091 CCUUCUCCUCGGGGCUCAG 2092NM_005080_275-293 GGAAACUGAAAAACAGAGU 2093 ACUCUGUUUUUCAGUUUCC 2094NM_005080_276-294 GAAACUGAAAAACAGAGUA 2095 UACUCUGUUUUUCAGUUUC 2096NM_005080_358-376 GAUUUAGAAGAAGAGAACC 2097 GGUUCUCUUCUUCUAAAUC 2098NM_005080_387-405 GCUAGAAAAUCAGCUUUUA 2099 UAAAAGCUGAUUUUCUAGC 2100NM_005080_628-646 UUGACUCUUCAGAUUCAGA 2101 UCUGAAUCUGAAGAGUCAA 2102NM_005080_656-674 CCUGUUGGGCAUUCUGGAC 2103 GUCCAGAAUGCCCAACAGG 2104NM_005080_719-737 UGCCAGCCUGGAGGAGCUC 2105 GAGCUCCUCCAGGCUGGCA 2106NM_005080_720-738 GCCAGCCUGGAGGAGCUCC 2107 GGAGCUCCUCCAGGCUGGC 2108NM_005080_721-739 CCAGCCUGGAGGAGCUCCC 2109 GGGAGCUCCUCCAGGCUGG 2110NM_005080_782-800 UUCUCUGUCAGUGGGGACG 2111 CGUCCCCACUGACAGAGAA 2112NM_005080_867-885 GUCUUAGAGAUACCCUCUG 2113 CAGAGGGUAUCUCUAAGAC 2114NM_005080_48-66 UAUGGUGGUGGUGGCAGCC 2115 GGCUGCCACCACCACCAUA 2116NM_005080_963-981 UUCAUUGUCUCAGUGAAGG 2117 CCUUCACUGAGACAAUGAA 2118 GeneXBP-1 reference transcript NM_005080 (human XBP-1 mRNA, FIG. 2) Notes19mers found in both human and rhesus

TABLE 9 XBP-1 human/Rhesus siRNAs with 3′ dinucleotide overhangs. sense(5′-3′) SEQ SEQ Oligo Name/location with 3′ dinucleotide ID antisense(5′-3′) ID of target sequence overhang NO: with 3′ dinucleotide overhangNO: NM_005080_390-408 AGAAAAUCAGCUUUUACGANN 2203 UCGUAAAAGCUGAUUUUCUNN2204 NM_005080_1184-1202 UCCCCAGCUGAUUAGUGUCNN 2205GACACUAAUCAGCUGGGGANN 2206 NM_005080_1494-1512 UACUUAUUAUGUAAGGGUCNN2207 GACCCUUACAUAAUAAGUANN 2208 NM_005080_1463-1481UAUCUUAAAAGGGUGGUAGNN 2209 CUACCACCCUUUUAAGAUANN 2210 NM_005080_610-628CCAUGGAUUCUGGCGGUAUNN 2211 AUACCGCCAGAAUCCAUGGNN 2212 NM_005080_823-841UUAAUGAACUAAUUCGUUUNN 2213 AAACGAAUUAGUUCAUUAANN 2214NM_005080_1507-1525 AGGGUCAUUAGACAAAUGUNN 2215 ACAUUUGUCUAAUGACCCUNN2216 NM_005080_827-845 UGAACUAAUUCGUUUUGACNN 2217 GUCAAAACGAAUUAGUUCANN2218 NM_005080_1503-1521 UGUAAGGGUCAUUAGACAANN 2219UUGUCUAAUGACCCUUACANN 2220 NM_005080_829-847 AACUAAUUCGUUUUGACCANN 2221UGGUCAAAACGAAUUAGUUNN 2222 NM_005080_1783-1801 UAUUUAAAACUACCCAUGCNN2223 GCAUGGGUAGUUUUAAAUANN 2224 NM_005080_1183-1201UUCCCCAGCUGAUUAGUGUNN 2225 ACACUAAUCAGCUGGGGAANN 2226NM_005080_1501-1519 UAUGUAAGGGUCAUUAGACNN 2227 GUCUAAUGACCCUUACAUANN2228 NM_005080_1504-1522 GUAAGGGUCAUUAGACAAANN 2229UUUGUCUAAUGACCCUUACNN 2230 NM_005080_734-752 GCUCCCAGAGGUCUACCCANN 2231UGGGUAGACCUCUGGGAGCNN 2232 NM_005080_893-911 GAGCCAAGCUAAUGUGGUANN 2233UACCACAUUAGCUUGGCUCNN 2234 NM_005080_1064-1082 CUGCCUACUGGAUGCUUACNN2235 GUAAGCAUCCAGUAGGCAGNN 2236 NM_005080_1066-1084GCCUACUGGAUGCUUACAGNN 2237 CUGUAAGCAUCCAGUAGGCNN 2238NM_005080_1136-1154 GCUUGGUGUAAACCAUUCUNN 2239 AGAAUGGUUUACACCAAGCNN2240 NM_005080_1137-1155 CUUGGUGUAAACCAUUCUUNN 2241AAGAAUGGUUUACACCAAGNN 2242 NM_005080_1182-1200 UUUCCCCAGCUGAUUAGUGNN2243 CACUAAUCAGCUGGGGAAANN 2244 NM_005080_1186-1204CCCAGCUGAUUAGUGUCUANN 2245 UAGACACUAAUCAGCUGGGNN 2246NM_005080_1189-1207 AGCUGAUUAGUGUCUAAGGNN 2247 CCUUAGACACUAAUCAGCUNN2248 NM_005080_1224-1242 UGCCCUUUUCCUUGACUAUNN 2249AUAGUCAAGGAAAAGGGCANN 2250 NM_005080_1229-1247 UUUUCCUUGACUAUUACACNN2251 GUGUAAUAGUCAAGGAAAANN 2252 NM_005080_1235-1253UUGACUAUUACACUGCCUGNN 2253 CAGGCAGUGUAAUAGUCAANN 2254NM_005080_1236-1254 UGACUAUUACACUGCCUGGNN 2255 CCAGGCAGUGUAAUAGUCANN2256 NM_005080_1438-1456 ACUACAGCUUUUAAGAUUGNN 2257CAAUCUUAAAAGCUGUAGUNN 2258 NM_005080_1441-1459 ACAGCUUUUAAGAUUGUACNN2259 GUACAAUCUUAAAAGCUGUNN 2260 NM_005080_1442-1460CAGCUUUUAAGAUUGUACUNN 2261 AGUACAAUCUUAAAAGCUGNN 2262NM_005080_1493-1511 AUACUUAUUAUGUAAGGGUNN 2263 ACCCUUACAUAAUAAGUAUNN2264 NM_005080_1502-1520 AUGUAAGGGUCAUUAGACANN 2265UGUCUAAUGACCCUUACAUNN 2266 NM_005080_1506-1524 AAGGGUCAUUAGACAAAUGNN2267 CAUUUGUCUAAUGACCCUUNN 2268 NM_005080_1594-1612UUGCCUCCAGUUUUAGGUCNN 2269 GACCUAAAACUGGAGGCAANN 2270NM_005080_1790-1808 AACUACCCAUGCAAUUAAANN 2271 UUUAAUUGCAUGGGUAGUUNN2272 NM_005080_304-322 ACUGCCAGAGAUCGAAAGANN 2273 UCUUUCGAUCUCUGGCAGUNN2274 NM_005080_305-323 CUGCCAGAGAUCGAAAGAANN 2275 UUCUUUCGAUCUCUGGCAGNN2276 NM_005080_395-413 AUCAGCUUUUACGAGAGAANN 2277 UUCUCUCGUAAAAGCUGAUNN2278 NM_005080_609-627 CCCAUGGAUUCUGGCGGUANN 2279 UACCGCCAGAAUCCAUGGGNN2280 NM_005080_611-629 CAUGGAUUCUGGCGGUAUUNN 2281 AAUACCGCCAGAAUCCAUGNN2282 NM_005080_617-635 UUCUGGCGGUAUUGACUCUNN 2283 AGAGUCAAUACCGCCAGAANN2284 NM_005080_621-639 GGCGGUAUUGACUCUUCAGNN 2285 CUGAAGAGUCAAUACCGCCNN2286 NM_005080_641-659 UUCAGAGUCUGAUAUCCUGNN 2287 CAGGAUAUCAGACUCUGAANN2288 NM_005080_648-666 UCUGAUAUCCUGUUGGGCANN 2289 UGCCCAACAGGAUAUCAGANN2290 NM_005080_651-669 GAUAUCCUGUUGGGCAUUCNN 2291 GAAUGCCCAACAGGAUAUCNN2292 NM_005080_735-753 CUCCCAGAGGUCUACCCAGNN 2293 CUGGGUAGACCUCUGGGAGNN2294 NM_005080_753-771 GAAGGACCCAGUUCCUUACNN 2295 GUAAGGAACUGGGUCCUUCNN2296 NM_005080_794-812 GGGGACGUCAUCAGCCAAGNN 2297 CUUGGCUGAUGACGUCCCCNN2298 NM_005080_826-844 AUGAACUAAUUCGUUUUGANN 2299 UCAAAACGAAUUAGUUCAUNN2300 NM_005080_836-854 UCGUUUUGACCACAUAUAUNN 2301 AUAUAUGUGGUCAAAACGANN2302 NM_005080_840-858 UUUGACCACAUAUAUACCANN 2303 UGGUAUAUAUGUGGUCAAANN2304 NM_005080_841-859 UUGACCACAUAUAUACCAANN 2305 UUGGUAUAUAUGUGGUCAANN2306 NM_005080_847-865 ACAUAUAUACCAAGCCCCUNN 2307 AGGGGCUUGGUAUAUAUGUNN2308 NM_005080_894-912 AGCCAAGCUAAUGUGGUAGNN 2309 CUACCACAUUAGCUUGGCUNN2310 NM_005080_895-913 GCCAAGCUAAUGUGGUAGUNN 2311 ACUACCACAUUAGCUUGGCNN2312 NM_005080_896-914 CCAAGCUAAUGUGGUAGUGNN 2313 CACUACCACAUUAGCUUGGNN2314 NM_005080_899-917 AGCUAAUGUGGUAGUGAAANN 2315 UUUCACUACCACAUUAGCUNN2316 NM_005080_908-926 GGUAGUGAAAAUCGAGGAANN 2317 UUCCUCGAUUUUCACUACCNN2318 NM_005080_917-935 AAUCGAGGAAGCACCUCUCNN 2319 GAGAGGUGCUUCCUCGAUUNN2320 NM_005080_937-955 GCCCCUCAGAGAAUGAUCANN 2321 UGAUCAUUCUCUGAGGGGCNN2322 NM_005080_950-968 UGAUCACCCUGAAUUCAUUNN 2323 AAUGAAUUCAGGGUGAUCANN2324 NM_005080_1185-1203 CCCCAGCUGAUUAGUGUCUNN 2325AGACACUAAUCAGCUGGGGNN 2326 NM_005080_1187-1205 CCAGCUGAUUAGUGUCUAANN2327 UUAGACACUAAUCAGCUGGNN 2328 NM_005080_1153-1171CUUGGGAGGACACUUUUGCNN 2329 GCAAAAGUGUCCUCCCAAGNN 2330NM_005080_1787-1805 UAAAACUACCCAUGCAAUUNN 2331 AAUUGCAUGGGUAGUUUUANN2332 NM_005080_606-624 CUCCCCAUGGAUUCUGGCGNN 2333 CGCCAGAAUCCAUGGGGAGNN2334 NM_005080_1019-1037 UAUCUCAAAUCUGCUUUCANN 2335UGAAAGCAGAUUUGAGAUANN 2336 NM_005080_1072-1090 UGGAUGCUUACAGUGACUGNN2337 CAGUCACUGUAAGCAUCCANN 2338 NM_005080_1228-1246CUUUUCCUUGACUAUUACANN 2339 UGUAAUAGUCAAGGAAAAGNN 2340NM_005080_1461-1479 UUUAUCUUAAAAGGGUGGUNN 2341 ACCACCCUUUUAAGAUAAANN2342 NM_005080_1495-1513 ACUUAUUAUGUAAGGGUCANN 2343UGACCCUUACAUAAUAAGUNN 2344 NM_005080_1496-1514 CUUAUUAUGUAAGGGUCAUNN2345 AUGACCCUUACAUAAUAAGNN 2346 NM_005080_1500-1518UUAUGUAAGGGUCAUUAGANN 2347 UCUAAUGACCCUUACAUAANN 2348NM_005080_1644-1662 CCUGCUGAGGGGGCUCUUUNN 2349 AAAGAGCCCCCUCAGCAGGNN2350 NM_005080_1708-1726 AUAGAAAUUUACUAUGUAANN 2351UUACAUAGUAAAUUUCUAUNN 2352 NM_005080_302-320 AGACUGCCAGAGAUCGAAANN 2353UUUCGAUCUCUGGCAGUCUNN 2354 NM_005080_607-625 UCCCCAUGGAUUCUGGCGGNN 2355CCGCCAGAAUCCAUGGGGANN 2356 NM_005080_824-842 UAAUGAACUAAUUCGUUUUNN 2357AAAACGAAUUAGUUCAUUANN 2358 NM_005080_953-971 UCACCCUGAAUUCAUUGUCNN 2359GACAAUGAAUUCAGGGUGANN 2360 NM_005080_1011-1029 GAGCUGGGUAUCUCAAAUCNN2361 GAUUUGAGAUACCCAGCUCNN 2362 NM_005080_1230-1248UUUCCUUGACUAUUACACUNN 2363 AGUGUAAUAGUCAAGGAAANN 2364NM_005080_1231-1249 UUCCUUGACUAUUACACUGNN 2365 CAGUGUAAUAGUCAAGGAANN2366 NM_005080_1290-1308 AAAGCCAAAAUAGAGAGUANN 2367UACUCUCUAUUUUGGCUUUNN 2368 NM_005080_1331-1349 AUUUGUUCAGAUCUCAUAGNN2369 CUAUGAGAUCUGAACAAAUNN 2370 NM_005080_1460-1478UUUUAUCUUAAAAGGGUGGNN 2371 CCACCCUUUUAAGAUAAAANN 2372NM_005080_1670-1688 GUAUACUUCAAGUAAGAUCNN 2373 GAUCUUACUUGAAGUAUACNN2374 NM_005080_1671-1689 UAUACUUCAAGUAAGAUCANN 2375UGAUCUUACUUGAAGUAUANN 2376 NM_005080_1735-1753 UGGAAUUUUUUCCUGCUAGNN2377 CUAGCAGGAAAAAAUUCCANN 2378 NM_005080_1744-1762UUCCUGCUAGUGUAGCUUCNN 2379 GAAGCUACACUAGCAGGAANN 2380NM_005080_1796-1814 CCAUGCAAUUAAAAGGUACNN 2381 GUACCUUUUAAUUGCAUGGNN2382 NM_005080_343-361 GAACAGCAAGUGGUAGAUUNN 2383 AAUCUACCACUUGCUGUUCNN2384 NM_005080_374-392 ACCAAAAACUUUUGCUAGANN 2385 UCUAGCAAAAGUUUUUGGUNN2386 NM_005080_375-393 CCAAAAACUUUUGCUAGAANN 2387 UUCUAGCAAAAGUUUUUGGNN2388 NM_005080_608-626 CCCCAUGGAUUCUGGCGGUNN 2389 ACCGCCAGAAUCCAUGGGGNN2390 NM_005080_652-670 AUAUCCUGUUGGGCAUUCUNN 2391 AGAAUGCCCAACAGGAUAUNN2392 NM_005080_686-704 AGUCAUGUUCUUCAAAUGCNN 2393 GCAUUUGAAGAACAUGACUNN2394 NM_005080_909-927 GUAGUGAAAAUCGAGGAAGNN 2395 CUUCCUCGAUUUUCACUACNN2396 NM_005080_951-969 GAUCACCCUGAAUUCAUUGNN 2397 CAAUGAAUUCAGGGUGAUCNN2398 NM_005080_952-970 AUCACCCUGAAUUCAUUGUNN 2399 ACAAUGAAUUCAGGGUGAUNN2400 NM_005080_825-843 AAUGAACUAAUUCGUUUUGNN 2401 CAAAACGAAUUAGUUCAUUNN2402 NM_005080_1194-1212 AUUAGUGUCUAAGGAAUGANN 2403UCAUUCCUUAGACACUAAUNN 2404 NM_005080_831-849 CUAAUUCGUUUUGACCACANN 2405UGUGGUCAAAACGAAUUAGNN 2406 NM_005080_835-853 UUCGUUUUGACCACAUAUANN 2407UAUAUGUGGUCAAAACGAANN 2408 NM_005080_869-887 CUUAGAGAUACCCUCUGAGNN 2409CUCAGAGGGUAUCUCUAAGNN 2410 NM_005080_1246-1264 ACUGCCUGGAGGAUAGCAGNN2411 CUGCUAUCCUCCAGGCAGUNN 2412 NM_005080_1453-1471AUUGUACUUUUAUCUUAAANN 2413 UUUAAGAUAAAAGUACAAUNN 2414NM_005080_1512-1530 CAUUAGACAAAUGUCUUGANN 2415 UCAAGACAUUUGUCUAAUGNN2416 NM_005080_1546-1564 UAUGAAUGGUUCUUUAUCANN 2417UGAUAAAGAACCAUUCAUANN 2418 NM_005080_1789-1807 AAACUACCCAUGCAAUUAANN2419 UUAAUUGCAUGGGUAGUUUNN 2420 NM_005080_325-343 GCUCGAAUGAGUGAGCUGGNN2421 CCAGCUCACUCAUUCGAGCNN 2422 NM_005080_393-411 AAAUCAGCUUUUACGAGAGNN2423 CUCUCGUAAAAGCUGAUUUNN 2424 NM_005080_788-806 GUCAGUGGGGACGUCAUCANN2425 UGAUGACGUCCCCACUGACNN 2426 NM_005080_821-839 CAUUAAUGAACUAAUUCGUNN2427 ACGAAUUAGUUCAUUAAUGNN 2428 NM_005080_1514-1532UUAGACAAAUGUCUUGAAGNN 2429 CUUCAAGACAUUUGUCUAANN 2430NM_005080_1797-1815 CAUGCAAUUAAAAGGUACANN 2431 UGUACCUUUUAAUUGCAUGNN2432 NM_005080_833-851 AAUUCGUUUUGACCACAUANN 2433 UAUGUGGUCAAAACGAAUUNN2434 NM_005080_1509-1527 GGUCAUUAGACAAAUGUCUNN 2435AGACAUUUGUCUAAUGACCNN 2436 NM_005080_1802-1820 AAUUAAAAGGUACAAUGCANN2437 UGCAUUGUACCUUUUAAUUNN 2438 NM_005080_391-409 GAAAAUCAGCUUUUACGAGNN2439 CUCGUAAAAGCUGAUUUUCNN 2440 NM_005080_843-861 GACCACAUAUAUACCAAGCNN2441 GCUUGGUAUAUAUGUGGUCNN 2442 NM_005080_1508-1526GGGUCAUUAGACAAAUGUCNN 2443 GACAUUUGUCUAAUGACCCNN 2444NM_005080_1754-1772 UGUAGCUUCUGAAAGGUGCNN 2445 GCACCUUUCAGAAGCUACANN2446 NM_005080_430-448 GUUGAGAACCAGGAGUUAANN 2447 UUAACUCCUGGUUCUCAACNN2448 NM_005080_437-455 ACCAGGAGUUAAGACAGCGNN 2449 CGCUGUCUUAACUCCUGGUNN2450 NM_005080_1465-1483 UCUUAAAAGGGUGGUAGUUNN 2451AACUACCACCCUUUUAAGANN 2452 NM_005080_1742-1760 UUUUCCUGCUAGUGUAGCUNN2453 AGCUACACUAGCAGGAAAANN 2454 NM_005080_438-456 CCAGGAGUUAAGACAGCGCNN2455 GCGCUGUCUUAACUCCUGGNN 2456 NM_005080_1060-1078CUUCCUGCCUACUGGAUGCNN 2457 GCAUCCAGUAGGCAGGAAGNN 2458NM_005080_1067-1085 CCUACUGGAUGCUUACAGUNN 2459 ACUGUAAGCAUCCAGUAGGNN2460 NM_005080_1197-1215 AGUGUCUAAGGAAUGAUCCNN 2461GGAUCAUUCCUUAGACACUNN 2462 NM_005080_1198-1216 GUGUCUAAGGAAUGAUCCANN2463 UGGAUCAUUCCUUAGACACNN 2464 NM_005080_1424-1442UACUAUAAUUGAGAACUACNN 2465 GUAGUUCUCAAUUAUAGUANN 2466NM_005080_1464-1482 AUCUUAAAAGGGUGGUAGUNN 2467 ACUACCACCCUUUUAAGAUNN2468 NM_005080_616-634 AUUCUGGCGGUAUUGACUCNN 2469 GAGUCAAUACCGCCAGAAUNN2470 NM_005080_757-775 GACCCAGUUCCUUACCAGCNN 2471 GCUGGUAAGGAACUGGGUCNN2472 NM_005080_785-803 UCUGUCAGUGGGGACGUCANN 2473 UGACGUCCCCACUGACAGANN2474 NM_005080_819-837 GCCAUUAAUGAACUAAUUCNN 2475 GAAUUAGUUCAUUAAUGGCNN2476 NM_005080_842-860 UGACCACAUAUAUACCAAGNN 2477 CUUGGUAUAUAUGUGGUCANN2478 NM_005080_845-863 CCACAUAUAUACCAAGCCCNN 2479 GGGCUUGGUAUAUAUGUGGNN2480 NM_005080_1013-1031 GCUGGGUAUCUCAAAUCUGNN 2481CAGAUUUGAGAUACCCAGCNN 2482 NM_005080_1431-1449 AUUGAGAACUACAGCUUUUNN2483 AAAAGCUGUAGUUCUCAAUNN 2484 NM_005080_1673-1691UACUUCAAGUAAGAUCAAGNN 2485 CUUGAUCUUACUUGAAGUANN 2486 NM_005080_283-301AAAAACAGAGUAGCAGCUCNN 2487 GAGCUGCUACUCUGUUUUUNN 2488 NM_005080_838-856GUUUUGACCACAUAUAUACNN 2489 GUAUAUAUGUGGUCAAAACNN 2490 NM_005080_279-297ACUGAAAAACAGAGUAGCANN 2491 UGCUACUCUGUUUUUCAGUNN 2492 NM_005080_633-651UCUUCAGAUUCAGAGUCUGNN 2493 CAGACUCUGAAUCUGAAGANN 2494NM_005080_1024-1042 CAAAUCUGCUUUCAUCCAGNN 2495 CUGGAUGAAAGCAGAUUUGNN2496 NM_005080_1147-1165 ACCAUUCUUGGGAGGACACNN 2497GUGUCCUCCCAAGAAUGGUNN 2498 NM_005080_1154-1172 UUGGGAGGACACUUUUGCCNN2499 GGCAAAAGUGUCCUCCCAANN 2500 NM_005080_1188-1206CAGCUGAUUAGUGUCUAAGNN 2501 CUUAGACACUAAUCAGCUGNN 2502NM_005080_1192-1210 UGAUUAGUGUCUAAGGAAUNN 2503 AUUCCUUAGACACUAAUCANN2504 NM_005080_1195-1213 UUAGUGUCUAAGGAAUGAUNN 2505AUCAUUCCUUAGACACUAANN 2506 NM_005080_1238-1256 ACUAUUACACUGCCUGGAGNN2507 CUCCAGGCAGUGUAAUAGUNN 2508 NM_005080_1548-1566UGAAUGGUUCUUUAUCAUUNN 2509 AAUGAUAAAGAACCAUUCANN 2510NM_005080_1549-1567 GAAUGGUUCUUUAUCAUUUNN 2511 AAAUGAUAAAGAACCAUUCNN2512 NM_005080_1677-1695 UCAAGUAAGAUCAAGAAUCNN 2513GAUUCUUGAUCUUACUUGANN 2514 NM_005080_1707-1725 UAUAGAAAUUUACUAUGUANN2515 UACAUAGUAAAUUUCUAUANN 2516 NM_005080_1713-1731AAUUUACUAUGUAAAUGCUNN 2517 AGCAUUUACAUAGUAAAUUNN 2518NM_005080_1786-1804 UUAAAACUACCCAUGCAAUNN 2519 AUUGCAUGGGUAGUUUUAANN2520 NM_005080_210-228 GCUGCCCCAGGCGCGCAAGNN 2521 CUUGCGCGCCUGGGGCAGCNN2522 NM_005080_278-296 AACUGAAAAACAGAGUAGCNN 2523 GCUACUCUGUUUUUCAGUUNN2524 NM_005080_284-302 AAAACAGAGUAGCAGCUCANN 2525 UGAGCUGCUACUCUGUUUUNN2526 NM_005080_290-308 GAGUAGCAGCUCAGACUGCNN 2527 GCAGUCUGAGCUGCUACUCNN2528 NM_005080_342-360 GGAACAGCAAGUGGUAGAUNN 2529 AUCUACCACUUGCUGUUCCNN2530 NM_005080_431-449 UUGAGAACCAGGAGUUAAGNN 2531 CUUAACUCCUGGUUCUCAANN2532 NM_005080_576-594 GCAGGCCCAGUUGUCACCCNN 2533 GGGUGACAACUGGGCCUGCNN2534 NM_005080_602-620 ACAUCUCCCCAUGGAUUCUNN 2535 AGAAUCCAUGGGGAGAUGUNN2536 NM_005080_618-636 UCUGGCGGUAUUGACUCUUNN 2537 AAGAGUCAAUACCGCCAGANN2538 NM_005080_678-696 UUGGACCCAGUCAUGUUCUNN 2539 AGAACAUGACUGGGUCCAANN2540 NM_005080_796-814 GGACGUCAUCAGCCAAGCUNN 2541 AGCUUGGCUGAUGACGUCCNN2542 NM_005080_940-958 CCUCAGAGAAUGAUCACCCNN 2543 GGGUGAUCAUUCUCUGAGGNN2544 NM_005080_954-972 CACCCUGAAUUCAUUGUCUNN 2545 AGACAAUGAAUUCAGGGUGNN2546 NM_005080_977-995 GAAGGAAGAACCUGUAGAANN 2547 UUCUACAGGUUCUUCCUUCNN2548 NM_005080_1018-1036 GUAUCUCAAAUCUGCUUUCNN 2549GAAAGCAGAUUUGAGAUACNN 2550 NM_005080_1026-1044 AAUCUGCUUUCAUCCAGCCNN2551 GGCUGGAUGAAAGCAGAUUNN 2552 NM_005080_1138-1156UUGGUGUAAACCAUUCUUGNN 2553 CAAGAAUGGUUUACACCAANN 2554NM_005080_1141-1159 GUGUAAACCAUUCUUGGGANN 2555 UCCCAAGAAUGGUUUACACNN2556 NM_005080_1142-1160 UGUAAACCAUUCUUGGGAGNN 2557CUCCCAAGAAUGGUUUACANN 2558 NM_005080_1155-1173 UGGGAGGACACUUUUGCCANN2559 UGGCAAAAGUGUCCUCCCANN 2560 NM_005080_1158-1176GAGGACACUUUUGCCAAUGNN 2561 CAUUGGCAAAAGUGUCCUCNN 2562NM_005080_1193-1211 GAUUAGUGUCUAAGGAAUGNN 2563 CAUUCCUUAGACACUAAUCNN2564 NM_005080_1196-1214 UAGUGUCUAAGGAAUGAUCNN 2565GAUCAUUCCUUAGACACUANN 2566 NM_005080_1219-1237 ACUGUUGCCCUUUUCCUUGNN2567 CAAGGAAAAGGGCAACAGUNN 2568 NM_005080_107-125 UGUCGGGGCAGCCCGCCUCNN2569 GAGGCGGGCUGCCCCGACANN 2570 NM_005080_108-126 GUCGGGGCAGCCCGCCUCCNN2571 GGAGGCGGGCUGCCCCGACNN 2572 NM_005080_1505-1523UAAGGGUCAUUAGACAAAUNN 2573 AUUUGUCUAAUGACCCUUANN 2574NM_005080_1567-1585 UCUCUUCCCCCUUUUUGGCNN 2575 GCCAAAAAGGGGGAAGAGANN2576 NM_005080_1672-1690 AUACUUCAAGUAAGAUCAANN 2577UUGAUCUUACUUGAAGUAUNN 2578 NM_005080_1678-1696 CAAGUAAGAUCAAGAAUCUNN2579 AGAUUCUUGAUCUUACUUGNN 2580 NM_005080_1778-1796CCAUUUAUUUAAAACUACCNN 2581 GGUAGUUUUAAAUAAAUGGNN 2582NM_005080_1779-1797 CAUUUAUUUAAAACUACCCNN 2583 GGGUAGUUUUAAAUAAAUGNN2584 NM_005080_280-298 CUGAAAAACAGAGUAGCAGNN 2585 CUGCUACUCUGUUUUUCAGNN2586 NM_005080_282-300 GAAAAACAGAGUAGCAGCUNN 2587 AGCUGCUACUCUGUUUUUCNN2588 NM_005080_288-306 CAGAGUAGCAGCUCAGACUNN 2589 AGUCUGAGCUGCUACUCUGNN2590 NM_005080_291-309 AGUAGCAGCUCAGACUGCCNN 2591 GGCAGUCUGAGCUGCUACUNN2592 NM_005080_347-365 AGCAAGUGGUAGAUUUAGANN 2593 UCUAAAUCUACCACUUGCUNN2594 NM_005080_397-415 CAGCUUUUACGAGAGAAAANN 2595 UUUUCUCUCGUAAAAGCUGNN2596 NM_005080_398-416 AGCUUUUACGAGAGAAAACNN 2597 GUUUUCUCUCGUAAAAGCUNN2598 NM_005080_399-417 GCUUUUACGAGAGAAAACUNN 2599 AGUUUUCUCUCGUAAAAGCNN2600 NM_005080_512-530 UGAGGCCAGUGGCCGGGUCNN 2601 GACCCGGCCACUGGCCUCANN2602 NM_005080_517-535 CCAGUGGCCGGGUCUGCUGNN 2603 CAGCAGACCCGGCCACUGGNN2604 NM_005080_596-614 UCCAGAACAUCUCCCCAUGNN 2605 CAUGGGGAGAUGUUCUGGANN2606 NM_005080_598-616 CAGAACAUCUCCCCAUGGANN 2607 UCCAUGGGGAGAUGUUCUGNN2608 NM_005080_601-619 AACAUCUCCCCAUGGAUUCNN 2609 GAAUCCAUGGGGAGAUGUUNN2610 NM_005080_605-623 UCUCCCCAUGGAUUCUGGCNN 2611 GCCAGAAUCCAUGGGGAGANN2612 NM_005080_661-679 UGGGCAUUCUGGACAACUUNN 2613 AAGUUGUCCAGAAUGCCCANN2614 NM_005080_688-706 UCAUGUUCUUCAAAUGCCCNN 2615 GGGCAUUUGAAGAACAUGANN2616 NM_005080_691-709 UGUUCUUCAAAUGCCCUUCNN 2617 GAAGGGCAUUUGAAGAACANN2618 NM_005080_828-846 GAACUAAUUCGUUUUGACCNN 2619 GGUCAAAACGAAUUAGUUCNN2620 NM_005080_830-848 ACUAAUUCGUUUUGACCACNN 2621 GUGGUCAAAACGAAUUAGUNN2622 NM_005080_834-852 AUUCGUUUUGACCACAUAUNN 2623 AUAUGUGGUCAAAACGAAUNN2624 NM_005080_846-864 CACAUAUAUACCAAGCCCCNN 2625 GGGGCUUGGUAUAUAUGUGNN2626 NM_005080_870-888 UUAGAGAUACCCUCUGAGANN 2627 UCUCAGAGGGUAUCUCUAANN2628 NM_005080_891-909 GAGAGCCAAGCUAAUGUGGNN 2629 CCACAUUAGCUUGGCUCUCNN2630 NM_005080_900-918 GCUAAUGUGGUAGUGAAAANN 2631 UUUUCACUACCACAUUAGCNN2632 NM_005080_911-929 AGUGAAAAUCGAGGAAGCANN 2633 UGCUUCCUCGAUUUUCACUNN2634 NM_005080_912-930 GUGAAAAUCGAGGAAGCACNN 2635 GUGCUUCCUCGAUUUUCACNN2636 NM_005080_979-997 AGGAAGAACCUGUAGAAGANN 2637 UCUUCUACAGGUUCUUCCUNN2638 NM_005080_1366-1384 GUCUUUUGACAUCCAGCAGNN 2639CUGCUGGAUGUCAAAAGACNN 2640 NM_005080_150-168 GGCCCUGCCGCUCAUGGUGNN 2641CACCAUGAGCGGCAGGGCCNN 2642 NM_005080_1437-1455 AACUACAGCUUUUAAGAUUNN2643 AAUCUUAAAAGCUGUAGUUNN 2644 NM_005080_482-500 AAGAGGAGGCGGAAGCCAANN2645 TTGGCTTCCGCCTCCTCTTNN 2646 NM_005080_580-598 GCCCAGUUGUCACCCCUCCNN2647 GGAGGGGUGACAACUGGGCNN 2648 NM_005080_613-631 UGGAUUCUGGCGGUAUUGANN2649 UCAAUACCGCCAGAAUCCANN 2650 NM_005080_1065-1083UGCCUACUGGAUGCUUACANN 2651 UGUAAGCAUCCAGUAGGCANN 2652 NM_005080_614-632GGAUUCUGGCGGUAUUGACNN 2653 GUCAAUACCGCCAGAAUCCNN 2654 NM_005080_640-658AUUCAGAGUCUGAUAUCCUNN 2655 AGGAUAUCAGACUCUGAAUNN 2656NM_005080_1014-1032 CUGGGUAUCUCAAAUCUGCNN 2657 GCAGAUUUGAGAUACCCAGNN2658 NM_005080_1015-1033 UGGGUAUCUCAAAUCUGCUNN 2659AGCAGAUUUGAGAUACCCANN 2660 NM_005080_1146-1164 AACCAUUCUUGGGAGGACANN2661 UGUCCUCCCAAGAAUGGUUNN 2662 NM_005080_1232-1250UCCUUGACUAUUACACUGCNN 2663 GCAGUGUAAUAGUCAAGGANN 2664NM_005080_1234-1252 CUUGACUAUUACACUGCCUNN 2665 AGGCAGUGUAAUAGUCAAGNN2666 NM_005080_1237-1255 GACUAUUACACUGCCUGGANN 2667UCCAGGCAGUGUAAUAGUCNN 2668 NM_005080_1443-1461 AGCUUUUAAGAUUGUACUUNN2669 AAGUACAAUCUUAAAAGCUNN 2670 NM_005080_1462-1480UUAUCUUAAAAGGGUGGUANN 2671 UACCACCCUUUUAAGAUAANN 2672NM_005080_1510-1528 GUCAUUAGACAAAUGUCUUNN 2673 AAGACAUUUGUCUAAUGACNN2674 NM_005080_1591-1609 GGCUUGCCUCCAGUUUUAGNN 2675CUAAAACUGGAGGCAAGCCNN 2676 NM_005080_1615-1633 UUAGUUUGCUUCUGUAAGCNN2677 GCUUACAGAAGCAAACUAANN 2678 NM_005080_1716-1734UUACUAUGUAAAUGCUUGANN 2679 UCAAGCAUUUACAUAGUAANN 2680NM_005080_1718-1736 ACUAUGUAAAUGCUUGAUGNN 2681 CAUCAAGCAUUUACAUAGUNN2682 NM_005080_1725-1743 AAAUGCUUGAUGGAAUUUUNN 2683AAAAUUCCAUCAAGCAUUUNN 2684 NM_005080_1748-1766 UGCUAGUGUAGCUUCUGAANN2685 UUCAGAAGCUACACUAGCANN 2686 NM_005080_1780-1798AUUUAUUUAAAACUACCCANN 2687 UGGGUAGUUUUAAAUAAAUNN 2688NM_005080_1794-1812 ACCCAUGCAAUUAAAAGGUNN 2689 ACCUUUUAAUUGCAUGGGUNN2690 NM_005080_156-174 GCCGCUCAUGGUGCCAGCCNN 2691 GGCUGGCACCAUGAGCGGCNN2692 NM_005080_299-317 CUCAGACUGCCAGAGAUCGNN 2693 CGAUCUCUGGCAGUCUGAGNN2694 NM_005080_344-362 AACAGCAAGUGGUAGAUUUNN 2695 AAAUCUACCACUUGCUGUUNN2696 NM_005080_371-389 AGAACCAAAAACUUUUGCUNN 2697 AGCAAAAGUUUUUGGUUCUNN2698 NM_005080_373-391 AACCAAAAACUUUUGCUAGNN 2699 CUAGCAAAAGUUUUUGGUUNN2700 NM_005080_524-542 CCGGGUCUGCUGAGUCCGCNN 2701 GCGGACUCAGCAGACCCGGNN2702 NM_005080_525-543 CGGGUCUGCUGAGUCCGCANN 2703 UGCGGACUCAGCAGACCCGNN2704 NM_005080_612-630 AUGGAUUCUGGCGGUAUUGNN 2705 CAAUACCGCCAGAAUCCAUNN2706 NM_005080_615-633 GAUUCUGGCGGUAUUGACUNN 2707 AGUCAAUACCGCCAGAAUCNN2708 NM_005080_645-663 GAGUCUGAUAUCCUGUUGGNN 2709 CCAACAGGAUAUCAGACUCNN2710 NM_005080_792-810 GUGGGGACGUCAUCAGCCANN 2711 UGGCUGAUGACGUCCCCACNN2712 NM_005080_905-923 UGUGGUAGUGAAAAUCGAGNN 2713 CUCGAUUUUCACUACCACANN2714 NM_005080_976-994 UGAAGGAAGAACCUGUAGANN 2715 UCUACAGGUUCUUCCUUCANN2716 NM_005080_1244-1262 ACACUGCCUGGAGGAUAGCNN 2717GCUAUCCUCCAGGCAGUGUNN 2718 NM_005080_1791-1809 ACUACCCAUGCAAUUAAAANN2719 UUUUAAUUGCAUGGGUAGUNN 2720 NM_005080_755-773 AGGACCCAGUUCCUUACCANN2721 UGGUAAGGAACUGGGUCCUNN 2722 NM_005080_799-817 CGUCAUCAGCCAAGCUGGANN2723 UCCAGCUUGGCUGAUGACGNN 2724 NM_005080_832-850 UAAUUCGUUUUGACCACAUNN2725 AUGUGGUCAAAACGAAUUANN 2726 NM_005080_839-857 UUUUGACCACAUAUAUACCNN2727 GGUAUAUAUGUGGUCAAAANN 2728 NM_005080_100-118 CUGCUUCUGUCGGGGCAGCNN2729 GCUGCCCCGACAGAAGCAGNN 2730 NM_005080_281-299 UGAAAAACAGAGUAGCAGCNN2731 GCUGCUACUCUGUUUUUCANN 2732 NM_005080_822-840 AUUAAUGAACUAAUUCGUUNN2733 AACGAAUUAGUUCAUUAAUNN 2734 NM_005080_1152-1170UCUUGGGAGGACACUUUUGNN 2735 CAAAAGUGUCCUCCCAAGANN 2736NM_005080_1191-1209 CUGAUUAGUGUCUAAGGAANN 2737 UUCCUUAGACACUAAUCAGNN2738 NM_005080_1225-1243 GCCCUUUUCCUUGACUAUUNN 2739AAUAGUCAAGGAAAAGGGCNN 2740 NM_005080_1227-1245 CCUUUUCCUUGACUAUUACNN2741 GUAAUAGUCAAGGAAAAGGNN 2742 NM_005080_1239-1257CUAUUACACUGCCUGGAGGNN 2743 CCUCCAGGCAGUGUAAUAGNN 2744NM_005080_1430-1448 AAUUGAGAACUACAGCUUUNN 2745 AAAGCUGUAGUUCUCAAUUNN2746 NM_005080_1499-1517 AUUAUGUAAGGGUCAUUAGNN 2747CUAAUGACCCUUACAUAAUNN 2748 NM_005080_1553-1571 GGUUCUUUAUCAUUUCUCUNN2749 AGAGAAAUGAUAAAGAACCNN 2750 NM_005080_1585-1603CAUCCUGGCUUGCCUCCAGNN 2751 CUGGAGGCAAGCCAGGAUGNN 2752NM_005080_1592-1610 GCUUGCCUCCAGUUUUAGGNN 2753 CCUAAAACUGGAGGCAAGCNN2754 NM_005080_1743-1761 UUUCCUGCUAGUGUAGCUUNN 2755AAGCUACACUAGCAGGAAANN 2756 NM_005080_154-172 CUGCCGCUCAUGGUGCCAGNN 2757CUGGCACCAUGAGCGGCAGNN 2758 NM_005080_193-211 GAGGCAGCGAGCGGGGGGCNN 2759GCCCCCCGCTCGCTGCCTCNN 2760 NM_005080_199-217 GCGAGCGGGGGGCUGCCCCNN 2761GGGGCAGCCCCCCGCUCGCNN 2762 NM_005080_292-310 GUAGCAGCUCAGACUGCCANN 2763UGGCAGUCUGAGCUGCUACNN 2764 NM_005080_341-359 UGGAACAGCAAGUGGUAGANN 2765UCUACCACUUGCUGUUCCANN 2766 NM_005080_377-395 AAAAACUUUUGCUAGAAAANN 2767UUUUCUAGCAAAAGUUUUUNN 2768 NM_005080_519-537 AGUGGCCGGGUCUGCUGAGNN 2769CUCAGCAGACCCGGCCACUNN 2770 NM_005080_522-540 GGCCGGGUCUGCUGAGUCCNN 2771GGACUCAGCAGACCCGGCCNN 2772 NM_005080_577-595 CAGGCCCAGUUGUCACCCCNN 2773GGGGUGACAACUGGGCCUGNN 2774 NM_005080_599-617 AGAACAUCUCCCCAUGGAUNN 2775AUCCAUGGGGAGAUGUUCUNN 2776 NM_005080_754-772 AAGGACCCAGUUCCUUACCNN 2777GGUAAGGAACUGGGUCCUUNN 2778 NM_005080_888-906 ACAGAGAGCCAAGCUAAUGNN 2779CAUUAGCUUGGCUCUCUGUNN 2780 NM_005080_939-957 CCCUCAGAGAAUGAUCACCNN 2781GGUGAUCAUUCUCUGAGGGNN 2782 NM_005080_964-982 UCAUUGUCUCAGUGAAGGANN 2783UCCUUCACUGAGACAAUGANN 2784 NM_005080_1012-1030 AGCUGGGUAUCUCAAAUCUNN2785 AGAUUUGAGAUACCCAGCUNN 2786 NM_005080_1016-1034GGGUAUCUCAAAUCUGCUUNN 2787 AAGCAGAUUUGAGAUACCCNN 2788NM_005080_1020-1038 AUCUCAAAUCUGCUUUCAUNN 2789 AUGAAAGCAGAUUUGAGAUNN2790 NM_005080_1025-1043 AAAUCUGCUUUCAUCCAGCNN 2791GCUGGAUGAAAGCAGAUUUNN 2792 NM_005080_1027-1045 AUCUGCUUUCAUCCAGCCANN2793 UGGCUGGAUGAAAGCAGAUNN 2794 NM_005080_1028-1046UCUGCUUUCAUCCAGCCACNN 2795 GUGGCUGGAUGAAAGCAGANN 2796NM_005080_1030-1048 UGCUUUCAUCCAGCCACUGNN 2797 CAGUGGCUGGAUGAAAGCANN2798 NM_005080_1031-1049 GCUUUCAUCCAGCCACUGCNN 2799GCAGUGGCUGGAUGAAAGCNN 2800 NM_005080_1032-1050 CUUUCAUCCAGCCACUGCCNN2801 GGCAGUGGCUGGAUGAAAGNN 2802 NM_005080_1033-1051UUUCAUCCAGCCACUGCCCNN 2803 GGGCAGUGGCUGGAUGAAANN 2804NM_005080_1056-1074 CCAUCUUCCUGCCUACUGGNN 2805 CCAGUAGGCAGGAAGAUGGNN2806 NM_005080_1057-1075 CAUCUUCCUGCCUACUGGANN 2807UCCAGUAGGCAGGAAGAUGNN 2808 NM_005080_1058-1076 AUCUUCCUGCCUACUGGAUNN2809 AUCCAGUAGGCAGGAAGAUNN 2810 NM_005080_1059-1077UCUUCCUGCCUACUGGAUGNN 2811 CAUCCAGUAGGCAGGAAGANN 2812NM_005080_1061-1079 UUCCUGCCUACUGGAUGCUNN 2813 AGCAUCCAGUAGGCAGGAANN2814 NM_005080_1063-1081 CCUGCCUACUGGAUGCUUANN 2815UAAGCAUCCAGUAGGCAGGNN 2816 NM_005080_1069-1087 UACUGGAUGCUUACAGUGANN2817 UCACUGUAAGCAUCCAGUANN 2818 NM_005080_1071-1089CUGGAUGCUUACAGUGACUNN 2819 AGUCACUGUAAGCAUCCAGNN 2820NM_005080_1073-1091 GGAUGCUUACAGUGACUGUNN 2821 ACAGUCACUGUAAGCAUCCNN2822 NM_005080_1075-1093 AUGCUUACAGUGACUGUGGNN 2823CCACAGUCACUGUAAGCAUNN 2824 NM_005080_1076-1094 UGCUUACAGUGACUGUGGANN2825 UCCACAGUCACUGUAAGCANN 2826 NM_005080_1078-1096CUUACAGUGACUGUGGAUANN 2827 UAUCCACAGUCACUGUAAGNN 2828NM_005080_1139-1157 UGGUGUAAACCAUUCUUGGNN 2829 CCAAGAAUGGUUUACACCANN2830 NM_005080_1140-1158 GGUGUAAACCAUUCUUGGGNN 2831CCCAAGAAUGGUUUACACCNN 2832 NM_005080_1143-1161 GUAAACCAUUCUUGGGAGGNN2833 CCUCCCAAGAAUGGUUUACNN 2834 NM_005080_1144-1162UAAACCAUUCUUGGGAGGANN 2835 UCCUCCCAAGAAUGGUUUANN 2836NM_005080_1145-1163 AAACCAUUCUUGGGAGGACNN 2837 GUCCUCCCAAGAAUGGUUUNN2838 NM_005080_1148-1166 CCAUUCUUGGGAGGACACUNN 2839AGUGUCCUCCCAAGAAUGGNN 2840 NM_005080_1156-1174 GGGAGGACACUUUUGCCAANN2841 UUGGCAAAAGUGUCCUCCCNN 2842 NM_005080_1157-1175GGAGGACACUUUUGCCAAUNN 2843 AUUGGCAAAAGUGUCCUCCNN 2844NM_005080_1159-1177 AGGACACUUUUGCCAAUGANN 2845 UCAUUGGCAAAAGUGUCCUNN2846 NM_005080_1160-1178 GGACACUUUUGCCAAUGAANN 2847UUCAUUGGCAAAAGUGUCCNN 2848 NM_005080_1190-1208 GCUGAUUAGUGUCUAAGGANN2849 UCCUUAGACACUAAUCAGCNN 2850 NM_005080_1218-1236UACUGUUGCCCUUUUCCUUNN 2851 AAGGAAAAGGGCAACAGUANN 2852NM_005080_1220-1238 CUGUUGCCCUUUUCCUUGANN 2853 UCAAGGAAAAGGGCAACAGNN2854 NM_005080_1221-1239 UGUUGCCCUUUUCCUUGACNN 2855GUCAAGGAAAAGGGCAACANN 2856 NM_005080_1233-1251 CCUUGACUAUUACACUGCCNN2857 GGCAGUGUAAUAGUCAAGGNN 2858 NM_005080_1240-1258UAUUACACUGCCUGGAGGANN 2859 UCCUCCAGGCAGUGUAAUANN 2860NM_005080_1241-1259 AUUACACUGCCUGGAGGAUNN 2861 AUCCUCCAGGCAGUGUAAUNN2862 NM_005080_1242-1260 UUACACUGCCUGGAGGAUANN 2863UAUCCUCCAGGCAGUGUAANN 2864 NM_005080_1243-1261 UACACUGCCUGGAGGAUAGNN2865 CUAUCCUCCAGGCAGUGUANN 2866 NM_005080_1282-1300UCAUUCAAAAAGCCAAAAUNN 2867 AUUUUGGCUUUUUGAAUGANN 2868NM_005080_1287-1305 CAAAAAGCCAAAAUAGAGANN 2869 UCUCUAUUUUGGCUUUUUGNN2870 NM_005080_1289-1307 AAAAGCCAAAAUAGAGAGUNN 2871ACUCUCUAUUUUGGCUUUUNN 2872 NM_005080_1310-1328 ACAGUCCUAGAGAAUUCCUNN2873 AGGAAUUCUCUAGGACUGUNN 2874 NM_005080_1330-1348UAUUUGUUCAGAUCUCAUANN 2875 UAUGAGAUCUGAACAAAUANN 2876NM_005080_1332-1350 UUUGUUCAGAUCUCAUAGANN 2877 UCUAUGAGAUCUGAACAAANN2878 NM_005080_1333-1351 UUGUUCAGAUCUCAUAGAUNN 2879AUCUAUGAGAUCUGAACAANN 2880 NM_005080_1369-1387 UUUUGACAUCCAGCAGUCCNN2881 GGACUGCUGGAUGUCAAAANN 2882 NM_005080_1370-1388UUUGACAUCCAGCAGUCCANN 2883 UGGACUGCUGGAUGUCAAANN 2884NM_005080_1371-1389 UUGACAUCCAGCAGUCCAANN 2885 UUGGACUGCUGGAUGUCAANN2886 NM_005080_101-119 UGCUUCUGUCGGGGCAGCCNN 2887 GGCUGCCCCGACAGAAGCANN2888 NM_005080_1418-1436 AAAUAUUACUAUAAUUGAGNN 2889CUCAAUUAUAGUAAUAUUUNN 2890 NM_005080_1419-1437 AAUAUUACUAUAAUUGAGANN2891 UCUCAAUUAUAGUAAUAUUNN 2892 NM_005080_1422-1440AUUACUAUAAUUGAGAACUNN 2893 AGUUCUCAAUUAUAGUAAUNN 2894 NM_005080_102-120GCUUCUGUCGGGGCAGCCCNN 2895 GGGCUGCCCCGACAGAAGCNN 2896NM_005080_1423-1441 UUACUAUAAUUGAGAACUANN 2897 UAGUUCUCAAUUAUAGUAANN2898 NM_005080_1425-1443 ACUAUAAUUGAGAACUACANN 2899UGUAGUUCUCAAUUAUAGUNN 2900 NM_005080_1427-1445 UAUAAUUGAGAACUACAGCNN2901 GCUGUAGUUCUCAAUUAUANN 2902 NM_005080_1428-1446AUAAUUGAGAACUACAGCUNN 2903 AGCUGUAGUUCUCAAUUAUNN 2904NM_005080_1429-1447 UAAUUGAGAACUACAGCUUNN 2905 AAGCUGUAGUUCUCAAUUANN2906 NM_005080_1432-1450 UUGAGAACUACAGCUUUUANN 2907UAAAAGCUGUAGUUCUCAANN 2908 NM_005080_1433-1451 UGAGAACUACAGCUUUUAANN2909 UUAAAAGCUGUAGUUCUCANN 2910 NM_005080_1435-1453AGAACUACAGCUUUUAAGANN 2911 UCUUAAAAGCUGUAGUUCUNN 2912NM_005080_1439-1457 CUACAGCUUUUAAGAUUGUNN 2913 ACAAUCUUAAAAGCUGUAGNN2914 NM_005080_104-122 UUCUGUCGGGGCAGCCCGCNN 2915 GCGGGCUGCCCCGACAGAANN2916 NM_005080_1444-1462 GCUUUUAAGAUUGUACUUUNN 2917AAAGUACAAUCUUAAAAGCNN 2918 NM_005080_1445-1463 CUUUUAAGAUUGUACUUUUNN2919 AAAAGUACAAUCUUAAAAGNN 2920 NM_005080_1446-1464UUUUAAGAUUGUACUUUUANN 2921 UAAAAGUACAAUCUUAAAANN 2922NM_005080_1447-1465 UUUAAGAUUGUACUUUUAUNN 2923 AUAAAAGUACAAUCUUAAANN2924 NM_005080_1448-1466 UUAAGAUUGUACUUUUAUCNN 2925GAUAAAAGUACAAUCUUAANN 2926 NM_005080_1451-1469 AGAUUGUACUUUUAUCUUANN2927 UAAGAUAAAAGUACAAUCUNN 2928 NM_005080_1454-1472UUGUACUUUUAUCUUAAAANN 2929 UUUUAAGAUAAAAGUACAANN 2930NM_005080_1458-1476 ACUUUUAUCUUAAAAGGGUNN 2931 ACCCUUUUAAGAUAAAAGUNN2932 NM_005080_1459-1477 CUUUUAUCUUAAAAGGGUGNN 2933CACCCUUUUAAGAUAAAAGNN 2934 NM_005080_106-124 CUGUCGGGGCAGCCCGCCUNN 2935AGGCGGGCUGCCCCGACAGNN 2936 NM_005080_1466-1484 CUUAAAAGGGUGGUAGUUUNN2937 AAACUACCACCCUUUUAAGNN 2938 NM_005080_1486-1504CCCUAAAAUACUUAUUAUGNN 2939 CAUAAUAAGUAUUUUAGGGNN 2940NM_005080_1487-1505 CCUAAAAUACUUAUUAUGUNN 2941 ACAUAAUAAGUAUUUUAGGNN2942 NM_005080_1489-1507 UAAAAUACUUAUUAUGUAANN 2943UUACAUAAUAAGUAUUUUANN 2944 NM_005080_1490-1508 AAAAUACUUAUUAUGUAAGNN2945 CUUACAUAAUAAGUAUUUUNN 2946 NM_005080_1491-1509AAAUACUUAUUAUGUAAGGNN 2947 CCUUACAUAAUAAGUAUUUNN 2948 NM_005080_109-127UCGGGGCAGCCCGCCUCCGNN 2949 CGGAGGCGGGCUGCCCCGANN 2950NM_005080_1497-1515 UUAUUAUGUAAGGGUCAUUNN 2951 AAUGACCCUUACAUAAUAANN2952 NM_005080_1498-1516 UAUUAUGUAAGGGUCAUUANN 2953UAAUGACCCUUACAUAAUANN 2954 NM_005080_110-128 CGGGGCAGCCCGCCUCCGCNN 2955GCGGAGGCGGGCUGCCCCGNN 2956 NM_005080_1511-1529 UCAUUAGACAAAUGUCUUGNN2957 CAAGACAUUUGUCUAAUGANN 2958 NM_005080_1513-1531AUUAGACAAAUGUCUUGAANN 2959 UUCAAGACAUUUGUCUAAUNN 2960NM_005080_1516-1534 AGACAAAUGUCUUGAAGUANN 2961 UACUUCAAGACAUUUGUCUNN2962 NM_005080_1517-1535 GACAAAUGUCUUGAAGUAGNN 2963CUACUUCAAGACAUUUGUCNN 2964 NM_005080_1518-1536 ACAAAUGUCUUGAAGUAGANN2965 UCUACUUCAAGACAUUUGUNN 2966 NM_005080_1547-1565AUGAAUGGUUCUUUAUCAUNN 2967 AUGAUAAAGAACCAUUCAUNN 2968NM_005080_1550-1568 AAUGGUUCUUUAUCAUUUCNN 2969 GAAAUGAUAAAGAACCAUUNN2970 NM_005080_1551-1569 AUGGUUCUUUAUCAUUUCUNN 2971AGAAAUGAUAAAGAACCAUNN 2972 NM_005080_1552-1570 UGGUUCUUUAUCAUUUCUCNN2973 GAGAAAUGAUAAAGAACCANN 2974 NM_005080_1554-1572GUUCUUUAUCAUUUCUCUUNN 2975 AAGAGAAAUGAUAAAGAACNN 2976NM_005080_1559-1577 UUAUCAUUUCUCUUCCCCCNN 2977 GGGGGAAGAGAAAUGAUAANN2978 NM_005080_1560-1578 UAUCAUUUCUCUUCCCCCUNN 2979AGGGGGAAGAGAAAUGAUANN 2980 NM_005080_1563-1581 CAUUUCUCUUCCCCCUUUUNN2981 AAAAGGGGGAAGAGAAAUGNN 2982 NM_005080_1565-1583UUUCUCUUCCCCCUUUUUGNN 2983 CAAAAAGGGGGAAGAGAAANN 2984NM_005080_1566-1584 UUCUCUUCCCCCUUUUUGGNN 2985 CCAAAAAGGGGGAAGAGAANN2986 NM_005080_1570-1588 CUUCCCCCUUUUUGGCAUCNN 2987GAUGCCAAAAAGGGGGAAGNN 2988 NM_005080_1573-1591 CCCCCUUUUUGGCAUCCUGNN2989 CAGGAUGCCAAAAAGGGGGNN 2990 NM_005080_1578-1596UUUUUGGCAUCCUGGCUUGNN 2991 CAAGCCAGGAUGCCAAAAANN 2992NM_005080_1579-1597 UUUUGGCAUCCUGGCUUGCNN 2993 GCAAGCCAGGAUGCCAAAANN2994 NM_005080_1580-1598 UUUGGCAUCCUGGCUUGCCNN 2995GGCAAGCCAGGAUGCCAAANN 2996 NM_005080_1581-1599 UUGGCAUCCUGGCUUGCCUNN2997 AGGCAAGCCAGGAUGCCAANN 2998 NM_005080_1583-1601GGCAUCCUGGCUUGCCUCCNN 2999 GGAGGCAAGCCAGGAUGCCNN 3000NM_005080_1584-1602 GCAUCCUGGCUUGCCUCCANN 3001 UGGAGGCAAGCCAGGAUGCNN3002 NM_005080_1586-1604 AUCCUGGCUUGCCUCCAGUNN 3003ACUGGAGGCAAGCCAGGAUNN 3004 NM_005080_1589-1607 CUGGCUUGCCUCCAGUUUUNN3005 AAAACUGGAGGCAAGCCAGNN 3006 NM_005080_1590-1608UGGCUUGCCUCCAGUUUUANN 3007 UAAAACUGGAGGCAAGCCANN 3008NM_005080_1595-1613 UGCCUCCAGUUUUAGGUCCNN 3009 GGACCUAAAACUGGAGGCANN3010 NM_005080_1616-1634 UAGUUUGCUUCUGUAAGCANN 3011UGCUUACAGAAGCAAACUANN 3012 NM_005080_1617-1635 AGUUUGCUUCUGUAAGCAANN3013 UUGCUUACAGAAGCAAACUNN 3014 NM_005080_1643-1661ACCUGCUGAGGGGGCUCUUNN 3015 AAGAGCCCCCUCAGCAGGUNN 3016NM_005080_1645-1663 CUGCUGAGGGGGCUCUUUCNN 3017 GAAAGAGCCCCCUCAGCAGNN3018 NM_005080_1646-1664 UGCUGAGGGGGCUCUUUCCNN 3019GGAAAGAGCCCCCUCAGCANN 3020 NM_005080_1647-1665 GCUGAGGGGGCUCUUUCCCNN3021 GGGAAAGAGCCCCCUCAGCNN 3022 NM_005080_1648-1666CUGAGGGGGCUCUUUCCCUNN 3023 AGGGAAAGAGCCCCCUCAGNN 3024NM_005080_1649-1667 UGAGGGGGCUCUUUCCCUCNN 3025 GAGGGAAAGAGCCCCCUCANN3026 NM_005080_1679-1697 AAGUAAGAUCAAGAAUCUUNN 3027AAGAUUCUUGAUCUUACUUNN 3028 NM_005080_1680-1698 AGUAAGAUCAAGAAUCUUUNN3029 AAAGAUUCUUGAUCUUACUNN 3030 NM_005080_1681-1699GUAAGAUCAAGAAUCUUUUNN 3031 AAAAGAUUCUUGAUCUUACNN 3032NM_005080_1682-1700 UAAGAUCAAGAAUCUUUUGNN 3033 CAAAAGAUUCUUGAUCUUANN3034 NM_005080_1683-1701 AAGAUCAAGAAUCUUUUGUNN 3035ACAAAAGAUUCUUGAUCUUNN 3036 NM_005080_1684-1702 AGAUCAAGAAUCUUUUGUGNN3037 CACAAAAGAUUCUUGAUCUNN 3038 NM_005080_1687-1705UCAAGAAUCUUUUGUGAAANN 3039 UUUCACAAAAGAUUCUUGANN 3040NM_005080_1709-1727 UAGAAAUUUACUAUGUAAANN 3041 UUUACAUAGUAAAUUUCUANN3042 NM_005080_1710-1728 AGAAAUUUACUAUGUAAAUNN 3043AUUUACAUAGUAAAUUUCUNN 3044 NM_005080_1711-1729 GAAAUUUACUAUGUAAAUGNN3045 CAUUUACAUAGUAAAUUUCNN 3046 NM_005080_1712-1730AAAUUUACUAUGUAAAUGCNN 3047 GCAUUUACAUAGUAAAUUUNN 3048NM_005080_1714-1732 AUUUACUAUGUAAAUGCUUNN 3049 AAGCAUUUACAUAGUAAAUNN3050 NM_005080_1715-1733 UUUACUAUGUAAAUGCUUGNN 3051CAAGCAUUUACAUAGUAAANN 3052 NM_005080_1717-1735 UACUAUGUAAAUGCUUGAUNN3053 AUCAAGCAUUUACAUAGUANN 3054 NM_005080_1719-1737CUAUGUAAAUGCUUGAUGGNN 3055 CCAUCAAGCAUUUACAUAGNN 3056NM_005080_1721-1739 AUGUAAAUGCUUGAUGGAANN 3057 UUCCAUCAAGCAUUUACAUNN3058 NM_005080_1722-1740 UGUAAAUGCUUGAUGGAAUNN 3059AUUCCAUCAAGCAUUUACANN 3060 NM_005080_1723-1741 GUAAAUGCUUGAUGGAAUUNN3061 AAUUCCAUCAAGCAUUUACNN 3062 NM_005080_1726-1744AAUGCUUGAUGGAAUUUUUNN 3063 AAAAAUUCCAUCAAGCAUUNN 3064NM_005080_1727-1745 AUGCUUGAUGGAAUUUUUUNN 3065 AAAAAAUUCCAUCAAGCAUNN3066 NM_005080_1728-1746 UGCUUGAUGGAAUUUUUUCNN 3067GAAAAAAUUCCAUCAAGCANN 3068 NM_005080_1729-1747 GCUUGAUGGAAUUUUUUCCNN3069 GGAAAAAAUUCCAUCAAGCNN 3070 NM_005080_1736-1754GGAAUUUUUUCCUGCUAGUNN 3071 ACUAGCAGGAAAAAAUUCCNN 3072NM_005080_1739-1757 AUUUUUUCCUGCUAGUGUANN 3073 UACACUAGCAGGAAAAAAUNN3074 NM_005080_1746-1764 CCUGCUAGUGUAGCUUCUGNN 3075CAGAAGCUACACUAGCAGGNN 3076 NM_005080_1747-1765 CUGCUAGUGUAGCUUCUGANN3077 UCAGAAGCUACACUAGCAGNN 3078 NM_005080_1749-1767GCUAGUGUAGCUUCUGAAANN 3079 UUUCAGAAGCUACACUAGCNN 3080NM_005080_1750-1768 CUAGUGUAGCUUCUGAAAGNN 3081 CUUUCAGAAGCUACACUAGNN3082 NM_005080_1751-1769 UAGUGUAGCUUCUGAAAGGNN 3083CCUUUCAGAAGCUACACUANN 3084 NM_005080_1752-1770 AGUGUAGCUUCUGAAAGGUNN3085 ACCUUUCAGAAGCUACACUNN 3086 NM_005080_1753-1771GUGUAGCUUCUGAAAGGUGNN 3087 CACCUUUCAGAAGCUACACNN 3088NM_005080_1755-1773 GUAGCUUCUGAAAGGUGCUNN 3089 AGCACCUUUCAGAAGCUACNN3090 NM_005080_1758-1776 GCUUCUGAAAGGUGCUUUCNN 3091GAAAGCACCUUUCAGAAGCNN 3092 NM_005080_1781-1799 UUUAUUUAAAACUACCCAUNN3093 AUGGGUAGUUUUAAAUAAANN 3094 NM_005080_1782-1800UUAUUUAAAACUACCCAUGNN 3095 CAUGGGUAGUUUUAAAUAANN 3096NM_005080_1784-1802 AUUUAAAACUACCCAUGCANN 3097 UGCAUGGGUAGUUUUAAAUNN3098 NM_005080_1785-1803 UUUAAAACUACCCAUGCAANN 3099UUGCAUGGGUAGUUUUAAANN 3100 NM_005080_1788-1806 AAAACUACCCAUGCAAUUANN3101 UAAUUGCAUGGGUAGUUUUNN 3102 NM_005080_1792-1810CUACCCAUGCAAUUAAAAGNN 3103 CUUUUAAUUGCAUGGGUAGNN 3104NM_005080_1793-1811 UACCCAUGCAAUUAAAAGGNN 3105 CCUUUUAAUUGCAUGGGUANN3106 NM_005080_1795-1813 CCCAUGCAAUUAAAAGGUANN 3107UACCUUUUAAUUGCAUGGGNN 3108 NM_005080_1798-1816 AUGCAAUUAAAAGGUACAANN3109 UUGUACCUUUUAAUUGCAUNN 3110 NM_005080_1799-1817UGCAAUUAAAAGGUACAAUNN 3111 AUUGUACCUUUUAAUUGCANN 3112NM_005080_1800-1818 GCAAUUAAAAGGUACAAUGNN 3113 CAUUGUACCUUUUAAUUGCNN3114 NM_005080_1801-1819 CAAUUAAAAGGUACAAUGCNN 3115GCAUUGUACCUUUUAAUUGNN 3116 NM_005080_146-164 GCCAGGCCCUGCCGCUCAUNN 3117AUGAGCGGCAGGGCCUGGCNN 3118 NM_005080_147-165 CCAGGCCCUGCCGCUCAUGNN 3119CAUGAGCGGCAGGGCCUGGNN 3120 NM_005080_148-166 CAGGCCCUGCCGCUCAUGGNN 3121CCAUGAGCGGCAGGGCCUGNN 3122 NM_005080_149-167 AGGCCCUGCCGCUCAUGGUNN 3123ACCAUGAGCGGCAGGGCCUNN 3124 NM_005080_155-173 UGCCGCUCAUGGUGCCAGCNN 3125GCUGGCACCAUGAGCGGCANN 3126 NM_005080_157-175 CCGCUCAUGGUGCCAGCCCNN 3127GGGCUGGCACCAUGAGCGGNN 3128 NM_005080_158-176 CGCUCAUGGUGCCAGCCCANN 3129UGGGCUGGCACCAUGAGCGNN 3130 NM_005080_159-177 GCUCAUGGUGCCAGCCCAGNN 3131CUGGGCUGGCACCAUGAGCNN 3132 NM_005080_188-206 GCCCGGAGGCAGCGAGCGGNN 3133CCGCTCGCTGCCTCCGGGCNN 3134 NM_005080_189-207 CCCGGAGGCAGCGAGCGGGNN 3135CCCGCTCGCTGCCTCCGGGNN 3136 NM_005080_195-213 GGCAGCGAGCGGGGGGCUGNN 3137CAGCCCCCCGCUCGCUGCCNN 3138 NM_005080_196-214 GCAGCGAGCGGGGGGCUGCNN 3139GCAGCCCCCCGCUCGCUGCNN 3140 NM_005080_197-215 CAGCGAGCGGGGGGCUGCCNN 3141GGCAGCCCCCCGCUCGCUGNN 3142 NM_005080_198-216 AGCGAGCGGGGGGCUGCCCNN 3143GGGCAGCCCCCCGCUCGCUNN 3144 NM_005080_205-223 GGGGGGCUGCCCCAGGCGCNN 3145GCGCCUGGGGCAGCCCCCCNN 3146 NM_005080_206-224 GGGGGCUGCCCCAGGCGCGNN 3147CGCGCCUGGGGCAGCCCCCNN 3148 NM_005080_207-225 GGGGCUGCCCCAGGCGCGCNN 3149GCGCGCCUGGGGCAGCCCCNN 3150 NM_005080_211-229 CUGCCCCAGGCGCGCAAGCNN 3151GCUUGCGCGCCUGGGGCAGNN 3152 NM_005080_250-268 AGCCCCGAGGAGAAGGCGCNN 3153GCGCCTTCTCCTCGGGGCTNN 3154 NM_005080_256-274 GAGGAGAAGGCGCUGAGGANN 3155UCCUCAGCGCCUUCUCCUCNN 3156 NM_005080_263-281 AGGCGCUGAGGAGGAAACUNN 3157AGUUUCCUCCUCAGCGCCUNN 3158 NM_005080_264-282 GGCGCUGAGGAGGAAACUGNN 3159CAGUUUCCUCCUCAGCGCCNN 3160 NM_005080_285-303 AAACAGAGUAGCAGCUCAGNN 3161CUGAGCUGCUACUCUGUUUNN 3162 NM_005080_286-304 AACAGAGUAGCAGCUCAGANN 3163UCUGAGCUGCUACUCUGUUNN 3164 NM_005080_287-305 ACAGAGUAGCAGCUCAGACNN 3165GUCUGAGCUGCUACUCUGUNN 3166 NM_005080_294-312 AGCAGCUCAGACUGCCAGANN 3167UCUGGCAGUCUGAGCUGCUNN 3168 NM_005080_295-313 GCAGCUCAGACUGCCAGAGNN 3169CUCUGGCAGUCUGAGCUGCNN 3170 NM_005080_296-314 CAGCUCAGACUGCCAGAGANN 3171UCUCUGGCAGUCUGAGCUGNN 3172 NM_005080_298-316 GCUCAGACUGCCAGAGAUCNN 3173GAUCUCUGGCAGUCUGAGCNN 3174 NM_005080_303-321 GACUGCCAGAGAUCGAAAGNN 3175CUUUCGAUCUCUGGCAGUCNN 3176 NM_005080_332-350 UGAGUGAGCUGGAACAGCANN 3177UGCUGUUCCAGCUCACUCANN 3178 NM_005080_339-357 GCUGGAACAGCAAGUGGUANN 3179UACCACUUGCUGUUCCAGCNN 3180 NM_005080_340-358 CUGGAACAGCAAGUGGUAGNN 3181CUACCACUUGCUGUUCCAGNN 3182 NM_005080_345-363 ACAGCAAGUGGUAGAUUUANN 3183UAAAUCUACCACUUGCUGUNN 3184 NM_005080_346-364 CAGCAAGUGGUAGAUUUAGNN 3185CUAAAUCUACCACUUGCUGNN 3186 NM_005080_348-366 GCAAGUGGUAGAUUUAGAANN 3187UUCUAAAUCUACCACUUGCNN 3188 NM_005080_349-367 CAAGUGGUAGAUUUAGAAGNN 3189CUUCUAAAUCUACCACUUGNN 3190 NM_005080_352-370 GUGGUAGAUUUAGAAGAAGNN 3191CUUCUUCUAAAUCUACCACNN 3192 NM_005080_353-371 UGGUAGAUUUAGAAGAAGANN 3193UCUUCUUCUAAAUCUACCANN 3194 NM_005080_354-372 GGUAGAUUUAGAAGAAGAGNN 3195CUCUUCUUCUAAAUCUACCNN 3196 NM_005080_355-373 GUAGAUUUAGAAGAAGAGANN 3197UCUCUUCUUCUAAAUCUACNN 3198 NM_005080_361-379 UUAGAAGAAGAGAACCAAANN 3199UUUGGUUCUCUUCUUCUAANN 3200 NM_005080_366-384 AGAAGAGAACCAAAAACUUNN 3201AAGUUUUUGGUUCUCUUCUNN 3202 NM_005080_369-387 AGAGAACCAAAAACUUUUGNN 3203CAAAAGUUUUUGGUUCUCUNN 3204 NM_005080_370-388 GAGAACCAAAAACUUUUGCNN 3205GCAAAAGUUUUUGGUUCUCNN 3206 NM_005080_372-390 GAACCAAAAACUUUUGCUANN 3207UAGCAAAAGUUUUUGGUUCNN 3208 NM_005080_376-394 CAAAAACUUUUGCUAGAAANN 3209UUUCUAGCAAAAGUUUUUGNN 3210 NM_005080_381-399 ACUUUUGCUAGAAAAUCAGNN 3211CUGAUUUUCUAGCAAAAGUNN 3212 NM_005080_384-402 UUUGCUAGAAAAUCAGCUUNN 3213AAGCUGAUUUUCUAGCAAANN 3214 NM_005080_388-406 CUAGAAAAUCAGCUUUUACNN 3215GUAAAAGCUGAUUUUCUAGNN 3216 NM_005080_392-410 AAAAUCAGCUUUUACGAGANN 3217UCUCGUAAAAGCUGAUUUUNN 3218 NM_005080_394-412 AAUCAGCUUUUACGAGAGANN 3219UCUCUCGUAAAAGCUGAUUNN 3220 NM_005080_396-414 UCAGCUUUUACGAGAGAAANN 3221UUUCUCUCGUAAAAGCUGANN 3222 NM_005080_400-418 CUUUUACGAGAGAAAACUCNN 3223GAGUUUUCUCUCGUAAAAGNN 3224 NM_005080_421-439 GGCCUUGUAGUUGAGAACCNN 3225GGUUCUCAACUACAAGGCCNN 3226 NM_005080_422-440 GCCUUGUAGUUGAGAACCANN 3227UGGUUCUCAACUACAAGGCNN 3228 NM_005080_423-441 CCUUGUAGUUGAGAACCAGNN 3229CUGGUUCUCAACUACAAGGNN 3230 NM_005080_425-443 UUGUAGUUGAGAACCAGGANN 3231UCCUGGUUCUCAACUACAANN 3232 NM_005080_428-446 UAGUUGAGAACCAGGAGUUNN 3233AACUCCUGGUUCUCAACUANN 3234 NM_005080_429-447 AGUUGAGAACCAGGAGUUANN 3235UAACUCCUGGUUCUCAACUNN 3236 NM_005080_432-450 UGAGAACCAGGAGUUAAGANN 3237UCUUAACUCCUGGUUCUCANN 3238 NM_005080_433-451 GAGAACCAGGAGUUAAGACNN 3239GUCUUAACUCCUGGUUCUCNN 3240 NM_005080_434-452 AGAACCAGGAGUUAAGACANN 3241UGUCUUAACUCCUGGUUCUNN 3242 NM_005080_435-453 GAACCAGGAGUUAAGACAGNN 3243CUGUCUUAACUCCUGGUUCNN 3244 NM_005080_436-454 AACCAGGAGUUAAGACAGCNN 3245GCUGUCUUAACUCCUGGUUNN 3246 NM_005080_459-477 GGGGAUGGAUGCCCUGGUUNN 3247AACCAGGGCAUCCAUCCCCNN 3248 NM_005080_460-478 GGGAUGGAUGCCCUGGUUGNN 3249CAACCAGGGCAUCCAUCCCNN 3250 NM_005080_462-480 GAUGGAUGCCCUGGUUGCUNN 3251AGCAACCAGGGCAUCCAUCNN 3252 NM_005080_486-504 GGAGGCGGAAGCCAAGGGGNN 3253CCCCTTGGCTTCCGCCTCCNN 3254 NM_005080_510-528 AGUGAGGCCAGUGGCCGGGNN 3255CCCGGCCACUGGCCUCACUNN 3256 NM_005080_513-531 GAGGCCAGUGGCCGGGUCUNN 3257AGACCCGGCCACUGGCCUCNN 3258 NM_005080_514-532 AGGCCAGUGGCCGGGUCUGNN 3259CAGACCCGGCCACUGGCCUNN 3260 NM_005080_515-533 GGCCAGUGGCCGGGUCUGCNN 3261GCAGACCCGGCCACUGGCCNN 3262 NM_005080_516-534 GCCAGUGGCCGGGUCUGCUNN 3263AGCAGACCCGGCCACUGGCNN 3264 NM_005080_520-538 GUGGCCGGGUCUGCUGAGUNN 3265ACUCAGCAGACCCGGCCACNN 3266 NM_005080_521-539 UGGCCGGGUCUGCUGAGUCNN 3267GACUCAGCAGACCCGGCCANN 3268 NM_005080_523-541 GCCGGGUCUGCUGAGUCCGNN 3269CGGACUCAGCAGACCCGGCNN 3270 NM_005080_578-596 AGGCCCAGUUGUCACCCCUNN 3271AGGGGUGACAACUGGGCCUNN 3272 NM_005080_581-599 CCCAGUUGUCACCCCUCCANN 3273UGGAGGGGUGACAACUGGGNN 3274 NM_005080_582-600 CCAGUUGUCACCCCUCCAGNN 3275CUGGAGGGGUGACAACUGGNN 3276 NM_005080_583-601 CAGUUGUCACCCCUCCAGANN 3277UCUGGAGGGGUGACAACUGNN 3278 NM_005080_584-602 AGUUGUCACCCCUCCAGAANN 3279UUCUGGAGGGGUGACAACUNN 3280 NM_005080_585-603 GUUGUCACCCCUCCAGAACNN 3281GUUCUGGAGGGGUGACAACNN 3282 NM_005080_586-604 UUGUCACCCCUCCAGAACANN 3283UGUUCUGGAGGGGUGACAANN 3284 NM_005080_587-605 UGUCACCCCUCCAGAACAUNN 3285AUGUUCUGGAGGGGUGACANN 3286 NM_005080_588-606 GUCACCCCUCCAGAACAUCNN 3287GAUGUUCUGGAGGGGUGACNN 3288 NM_005080_589-607 UCACCCCUCCAGAACAUCUNN 3289AGAUGUUCUGGAGGGGUGANN 3290 NM_005080_590-608 CACCCCUCCAGAACAUCUCNN 3291GAGAUGUUCUGGAGGGGUGNN 3292 NM_005080_591-609 ACCCCUCCAGAACAUCUCCNN 3293GGAGAUGUUCUGGAGGGGUNN 3294 NM_005080_597-615 CCAGAACAUCUCCCCAUGGNN 3295CCAUGGGGAGAUGUUCUGGNN 3296 NM_005080_600-618 GAACAUCUCCCCAUGGAUUNN 3297AAUCCAUGGGGAGAUGUUCNN 3298 NM_005080_603-621 CAUCUCCCCAUGGAUUCUGNN 3299CAGAAUCCAUGGGGAGAUGNN 3300 NM_005080_619-637 CUGGCGGUAUUGACUCUUCNN 3301GAAGAGUCAAUACCGCCAGNN 3302 NM_005080_620-638 UGGCGGUAUUGACUCUUCANN 3303UGAAGAGUCAAUACCGCCANN 3304 NM_005080_622-640 GCGGUAUUGACUCUUCAGANN 3305UCUGAAGAGUCAAUACCGCNN 3306 NM_005080_623-641 CGGUAUUGACUCUUCAGAUNN 3307AUCUGAAGAGUCAAUACCGNN 3308 NM_005080_624-642 GGUAUUGACUCUUCAGAUUNN 3309AAUCUGAAGAGUCAAUACCNN 3310 NM_005080_625-643 GUAUUGACUCUUCAGAUUCNN 3311GAAUCUGAAGAGUCAAUACNN 3312 NM_005080_626-644 UAUUGACUCUUCAGAUUCANN 3313UGAAUCUGAAGAGUCAAUANN 3314 NM_005080_629-647 UGACUCUUCAGAUUCAGAGNN 3315CUCUGAAUCUGAAGAGUCANN 3316 NM_005080_632-650 CUCUUCAGAUUCAGAGUCUNN 3317AGACUCUGAAUCUGAAGAGNN 3318 NM_005080_634-652 CUUCAGAUUCAGAGUCUGANN 3319UCAGACUCUGAAUCUGAAGNN 3320 NM_005080_637-655 CAGAUUCAGAGUCUGAUAUNN 3321AUAUCAGACUCUGAAUCUGNN 3322 NM_005080_638-656 AGAUUCAGAGUCUGAUAUCNN 3323GAUAUCAGACUCUGAAUCUNN 3324 NM_005080_639-657 GAUUCAGAGUCUGAUAUCCNN 3325GGAUAUCAGACUCUGAAUCNN 3326 NM_005080_642-660 UCAGAGUCUGAUAUCCUGUNN 3327ACAGGAUAUCAGACUCUGANN 3328 NM_005080_643-661 CAGAGUCUGAUAUCCUGUUNN 3329AACAGGAUAUCAGACUCUGNN 3330 NM_005080_644-662 AGAGUCUGAUAUCCUGUUGNN 3331CAACAGGAUAUCAGACUCUNN 3332 NM_005080_646-664 AGUCUGAUAUCCUGUUGGGNN 3333CCCAACAGGAUAUCAGACUNN 3334 NM_005080_649-667 CUGAUAUCCUGUUGGGCAUNN 3335AUGCCCAACAGGAUAUCAGNN 3336 NM_005080_650-668 UGAUAUCCUGUUGGGCAUUNN 3337AAUGCCCAACAGGAUAUCANN 3338 NM_005080_653-671 UAUCCUGUUGGGCAUUCUGNN 3339CAGAAUGCCCAACAGGAUANN 3340 NM_005080_658-676 UGUUGGGCAUUCUGGACAANN 3341UUGUCCAGAAUGCCCAACANN 3342 NM_005080_659-677 GUUGGGCAUUCUGGACAACNN 3343GUUGUCCAGAAUGCCCAACNN 3344 NM_005080_660-678 UUGGGCAUUCUGGACAACUNN 3345AGUUGUCCAGAAUGCCCAANN 3346 NM_005080_663-681 GGCAUUCUGGACAACUUGGNN 3347CCAAGUUGUCCAGAAUGCCNN 3348 NM_005080_664-682 GCAUUCUGGACAACUUGGANN 3349UCCAAGUUGUCCAGAAUGCNN 3350 NM_005080_668-686 UCUGGACAACUUGGACCCANN 3351UGGGUCCAAGUUGUCCAGANN 3352 NM_005080_671-689 GGACAACUUGGACCCAGUCNN 3353GACUGGGUCCAAGUUGUCCNN 3354 NM_005080_676-694 ACUUGGACCCAGUCAUGUUNN 3355AACAUGACUGGGUCCAAGUNN 3356 NM_005080_677-695 CUUGGACCCAGUCAUGUUCNN 3357GAACAUGACUGGGUCCAAGNN 3358 NM_005080_679-697 UGGACCCAGUCAUGUUCUUNN 3359AAGAACAUGACUGGGUCCANN 3360 NM_005080_680-698 GGACCCAGUCAUGUUCUUCNN 3361GAAGAACAUGACUGGGUCCNN 3362 NM_005080_682-700 ACCCAGUCAUGUUCUUCAANN 3363UUGAAGAACAUGACUGGGUNN 3364 NM_005080_687-705 GUCAUGUUCUUCAAAUGCCNN 3365GGCAUUUGAAGAACAUGACNN 3366 NM_005080_689-707 CAUGUUCUUCAAAUGCCCUNN 3367AGGGCAUUUGAAGAACAUGNN 3368 NM_005080_695-713 CUUCAAAUGCCCUUCCCCANN 3369UGGGGAAGGGCAUUUGAAGNN 3370 NM_005080_696-714 UUCAAAUGCCCUUCCCCAGNN 3371CUGGGGAAGGGCAUUUGAANN 3372 NM_005080_698-716 CAAAUGCCCUUCCCCAGAGNN 3373CUCUGGGGAAGGGCAUUUGNN 3374 NM_005080_731-749 GGAGCUCCCAGAGGUCUACNN 3375GUAGACCUCUGGGAGCUCCNN 3376 NM_005080_732-750 GAGCUCCCAGAGGUCUACCNN 3377GGUAGACCUCUGGGAGCUCNN 3378 NM_005080_733-751 AGCUCCCAGAGGUCUACCCNN 3379GGGUAGACCUCUGGGAGCUNN 3380 NM_005080_736-754 UCCCAGAGGUCUACCCAGANN 3381UCUGGGUAGACCUCUGGGANN 3382 NM_005080_737-755 CCCAGAGGUCUACCCAGAANN 3383UUCUGGGUAGACCUCUGGGNN 3384 NM_005080_738-756 CCAGAGGUCUACCCAGAAGNN 3385CUUCUGGGUAGACCUCUGGNN 3386 NM_005080_740-758 AGAGGUCUACCCAGAAGGANN 3387UCCUUCUGGGUAGACCUCUNN 3388 NM_005080_741-759 GAGGUCUACCCAGAAGGACNN 3389GUCCUUCUGGGUAGACCUCNN 3390 NM_005080_742-760 AGGUCUACCCAGAAGGACCNN 3391GGUCCUUCUGGGUAGACCUNN 3392 NM_005080_743-761 GGUCUACCCAGAAGGACCCNN 3393GGGUCCUUCUGGGUAGACCNN 3394 NM_005080_748-766 ACCCAGAAGGACCCAGUUCNN 3395GAACUGGGUCCUUCUGGGUNN 3396 NM_005080_749-767 CCCAGAAGGACCCAGUUCCNN 3397GGAACUGGGUCCUUCUGGGNN 3398 NM_005080_750-768 CCAGAAGGACCCAGUUCCUNN 3399AGGAACUGGGUCCUUCUGGNN 3400 NM_005080_751-769 CAGAAGGACCCAGUUCCUUNN 3401AAGGAACUGGGUCCUUCUGNN 3402 NM_005080_752-770 AGAAGGACCCAGUUCCUUANN 3403UAAGGAACUGGGUCCUUCUNN 3404 NM_005080_756-774 GGACCCAGUUCCUUACCAGNN 3405CUGGUAAGGAACUGGGUCCNN 3406 NM_005080_758-776 ACCCAGUUCCUUACCAGCCNN 3407GGCUGGUAAGGAACUGGGUNN 3408 NM_005080_759-777 CCCAGUUCCUUACCAGCCUNN 3409AGGCUGGUAAGGAACUGGGNN 3410 NM_005080_760-778 CCAGUUCCUUACCAGCCUCNN 3411GAGGCUGGUAAGGAACUGGNN 3412 NM_005080_761-779 CAGUUCCUUACCAGCCUCCNN 3413GGAGGCUGGUAAGGAACUGNN 3414 NM_005080_762-780 AGUUCCUUACCAGCCUCCCNN 3415GGGAGGCUGGUAAGGAACUNN 3416 NM_005080_767-785 CUUACCAGCCUCCCUUUCUNN 3417AGAAAGGGAGGCUGGUAAGNN 3418 NM_005080_769-787 UACCAGCCUCCCUUUCUCUNN 3419AGAGAAAGGGAGGCUGGUANN 3420 NM_005080_773-791 AGCCUCCCUUUCUCUGUCANN 3421UGACAGAGAAAGGGAGGCUNN 3422 NM_005080_779-797 CCUUUCUCUGUCAGUGGGGNN 3423CCCCACUGACAGAGAAAGGNN 3424 NM_005080_786-804 CUGUCAGUGGGGACGUCAUNN 3425AUGACGUCCCCACUGACAGNN 3426 NM_005080_787-805 UGUCAGUGGGGACGUCAUCNN 3427GAUGACGUCCCCACUGACANN 3428 NM_005080_789-807 UCAGUGGGGACGUCAUCAGNN 3429CUGAUGACGUCCCCACUGANN 3430 NM_005080_793-811 UGGGGACGUCAUCAGCCAANN 3431UUGGCUGAUGACGUCCCCANN 3432 NM_005080_795-813 GGGACGUCAUCAGCCAAGCNN 3433GCUUGGCUGAUGACGUCCCNN 3434 NM_005080_797-815 GACGUCAUCAGCCAAGCUGNN 3435CAGCUUGGCUGAUGACGUCNN 3436 NM_005080_798-816 ACGUCAUCAGCCAAGCUGGNN 3437CCAGCUUGGCUGAUGACGUNN 3438 NM_005080_800-818 GUCAUCAGCCAAGCUGGAANN 3439UUCCAGCUUGGCUGAUGACNN 3440 NM_005080_804-822 UCAGCCAAGCUGGAAGCCANN 3441UGGCUUCCAGCUUGGCUGANN 3442 NM_005080_806-824 AGCCAAGCUGGAAGCCAUUNN 3443AAUGGCUUCCAGCUUGGCUNN 3444 NM_005080_807-825 GCCAAGCUGGAAGCCAUUANN 3445UAAUGGCUUCCAGCUUGGCNN 3446 NM_005080_808-826 CCAAGCUGGAAGCCAUUAANN 3447UUAAUGGCUUCCAGCUUGGNN 3448 NM_005080_809-827 CAAGCUGGAAGCCAUUAAUNN 3449AUUAAUGGCUUCCAGCUUGNN 3450 NM_005080_810-828 AAGCUGGAAGCCAUUAAUGNN 3451CAUUAAUGGCUUCCAGCUUNN 3452 NM_005080_811-829 AGCUGGAAGCCAUUAAUGANN 3453UCAUUAAUGGCUUCCAGCUNN 3454 NM_005080_813-831 CUGGAAGCCAUUAAUGAACNN 3455GUUCAUUAAUGGCUUCCAGNN 3456 NM_005080_814-832 UGGAAGCCAUUAAUGAACUNN 3457AGUUCAUUAAUGGCUUCCANN 3458 NM_005080_818-836 AGCCAUUAAUGAACUAAUUNN 3459AAUUAGUUCAUUAAUGGCUNN 3460 NM_005080_820-838 CCAUUAAUGAACUAAUUCGNN 3461CGAAUUAGUUCAUUAAUGGNN 3462 NM_005080_837-855 CGUUUUGACCACAUAUAUANN 3463UAUAUAUGUGGUCAAAACGNN 3464 NM_005080_844-862 ACCACAUAUAUACCAAGCCNN 3465GGCUUGGUAUAUAUGUGGUNN 3466 NM_005080_872-890 AGAGAUACCCUCUGAGACANN 3467UGUCUCAGAGGGUAUCUCUNN 3468 NM_005080_873-891 GAGAUACCCUCUGAGACAGNN 3469CUGUCUCAGAGGGUAUCUCNN 3470 NM_005080_874-892 AGAUACCCUCUGAGACAGANN 3471UCUGUCUCAGAGGGUAUCUNN 3472 NM_005080_876-894 AUACCCUCUGAGACAGAGANN 3473UCUCUGUCUCAGAGGGUAUNN 3474 NM_005080_889-907 CAGAGAGCCAAGCUAAUGUNN 3475ACAUUAGCUUGGCUCUCUGNN 3476 NM_005080_890-908 AGAGAGCCAAGCUAAUGUGNN 3477CACAUUAGCUUGGCUCUCUNN 3478 NM_005080_897-915 CAAGCUAAUGUGGUAGUGANN 3479UCACUACCACAUUAGCUUGNN 3480 NM_005080_898-916 AAGCUAAUGUGGUAGUGAANN 3481UUCACUACCACAUUAGCUUNN 3482 NM_005080_901-919 CUAAUGUGGUAGUGAAAAUNN 3483AUUUUCACUACCACAUUAGNN 3484 NM_005080_903-921 AAUGUGGUAGUGAAAAUCGNN 3485CGAUUUUCACUACCACAUUNN 3486 NM_005080_904-922 AUGUGGUAGUGAAAAUCGANN 3487UCGAUUUUCACUACCACAUNN 3488 NM_005080_906-924 GUGGUAGUGAAAAUCGAGGNN 3489CCUCGAUUUUCACUACCACNN 3490 NM_005080_907-925 UGGUAGUGAAAAUCGAGGANN 3491UCCUCGAUUUUCACUACCANN 3492 NM_005080_910-928 UAGUGAAAAUCGAGGAAGCNN 3493GCUUCCUCGAUUUUCACUANN 3494 NM_005080_913-931 UGAAAAUCGAGGAAGCACCNN 3495GGUGCUUCCUCGAUUUUCANN 3496 NM_005080_916-934 AAAUCGAGGAAGCACCUCUNN 3497AGAGGUGCUUCCUCGAUUUNN 3498 NM_005080_918-936 AUCGAGGAAGCACCUCUCANN 3499UGAGAGGUGCUUCCUCGAUNN 3500 NM_005080_919-937 UCGAGGAAGCACCUCUCAGNN 3501CUGAGAGGUGCUUCCUCGANN 3502 NM_005080_920-938 CGAGGAAGCACCUCUCAGCNN 3503GCUGAGAGGUGCUUCCUCGNN 3504 NM_005080_922-940 AGGAAGCACCUCUCAGCCCNN 3505GGGCUGAGAGGUGCUUCCUNN 3506 NM_005080_923-941 GGAAGCACCUCUCAGCCCCNN 3507GGGGCUGAGAGGUGCUUCCNN 3508 NM_005080_929-947 ACCUCUCAGCCCCUCAGAGNN 3509CUCUGAGGGGCUGAGAGGUNN 3510 NM_005080_930-948 CCUCUCAGCCCCUCAGAGANN 3511UCUCUGAGGGGCUGAGAGGNN 3512 NM_005080_931-949 CUCUCAGCCCCUCAGAGAANN 3513UUCUCUGAGGGGCUGAGAGNN 3514 NM_005080_932-950 UCUCAGCCCCUCAGAGAAUNN 3515AUUCUCUGAGGGGCUGAGANN 3516 NM_005080_933-951 CUCAGCCCCUCAGAGAAUGNN 3517CAUUCUCUGAGGGGCUGAGNN 3518 NM_005080_934-952 UCAGCCCCUCAGAGAAUGANN 3519UCAUUCUCUGAGGGGCUGANN 3520 NM_005080_935-953 CAGCCCCUCAGAGAAUGAUNN 3521AUCAUUCUCUGAGGGGCUGNN 3522 NM_005080_936-954 AGCCCCUCAGAGAAUGAUCNN 3523GAUCAUUCUCUGAGGGGCUNN 3524 NM_005080_938-956 CCCCUCAGAGAAUGAUCACNN 3525GUGAUCAUUCUCUGAGGGGNN 3526 NM_005080_941-959 CUCAGAGAAUGAUCACCCUNN 3527AGGGUGAUCAUUCUCUGAGNN 3528 NM_005080_942-960 UCAGAGAAUGAUCACCCUGNN 3529CAGGGUGAUCAUUCUCUGANN 3530 NM_005080_943-961 CAGAGAAUGAUCACCCUGANN 3531UCAGGGUGAUCAUUCUCUGNN 3532 NM_005080_944-962 AGAGAAUGAUCACCCUGAANN 3533UUCAGGGUGAUCAUUCUCUNN 3534 NM_005080_946-964 AGAAUGAUCACCCUGAAUUNN 3535AAUUCAGGGUGAUCAUUCUNN 3536 NM_005080_947-965 GAAUGAUCACCCUGAAUUCNN 3537GAAUUCAGGGUGAUCAUUCNN 3538 NM_005080_948-966 AAUGAUCACCCUGAAUUCANN 3539UGAAUUCAGGGUGAUCAUUNN 3540 NM_005080_949-967 AUGAUCACCCUGAAUUCAUNN 3541AUGAAUUCAGGGUGAUCAUNN 3542 NM_005080_955-973 ACCCUGAAUUCAUUGUCUCNN 3543GAGACAAUGAAUUCAGGGUNN 3544 NM_005080_956-974 CCCUGAAUUCAUUGUCUCANN 3545UGAGACAAUGAAUUCAGGGNN 3546 NM_005080_957-975 CCUGAAUUCAUUGUCUCAGNN 3547CUGAGACAAUGAAUUCAGGNN 3548 NM_005080_960-978 GAAUUCAUUGUCUCAGUGANN 3549UCACUGAGACAAUGAAUUCNN 3550 NM_005080_961-979 AAUUCAUUGUCUCAGUGAANN 3551UUCACUGAGACAAUGAAUUNN 3552 NM_005080_965-983 CAUUGUCUCAGUGAAGGAANN 3553UUCCUUCACUGAGACAAUGNN 3554 NM_005080_967-985 UUGUCUCAGUGAAGGAAGANN 3555UCUUCCUUCACUGAGACAANN 3556 NM_005080_968-986 UGUCUCAGUGAAGGAAGAANN 3557UUCUUCCUUCACUGAGACANN 3558 NM_005080_971-989 CUCAGUGAAGGAAGAACCUNN 3559AGGUUCUUCCUUCACUGAGNN 3560 NM_005080_972-990 UCAGUGAAGGAAGAACCUGNN 3561CAGGUUCUUCCUUCACUGANN 3562 NM_005080_973-991 CAGUGAAGGAAGAACCUGUNN 3563ACAGGUUCUUCCUUCACUGNN 3564 NM_005080_980-998 GGAAGAACCUGUAGAAGAUNN 3565AUCUUCUACAGGUUCUUCCNN 3566 NM_005080_984-1002 GAACCUGUAGAAGAUGACCNN 3567GGUCAUCUUCUACAGGUUCNN 3568 NM_005080_986-1004 ACCUGUAGAAGAUGACCUCNN 3569GAGGUCAUCUUCUACAGGUNN 3570 NM_005080_1023-1041 UCAAAUCUGCUUUCAUCCANN3571 UGGAUGAAAGCAGAUUUGANN 3572 NM_005080_1151-1169UUCUUGGGAGGACACUUUUNN 3573 AAAAGUGUCCUCCCAAGAANN 3574NM_005080_1367-1385 UCUUUUGACAUCCAGCAGUNN 3575 ACUGCUGGAUGUCAAAAGANN3576 NM_005080_1414-1432 UAAGAAAUAUUACUAUAAUNN 3577AUUAUAGUAAUAUUUCUUANN 3578 NM_005080_1415-1433 AAGAAAUAUUACUAUAAUUNN3579 AAUUAUAGUAAUAUUUCUUNN 3580 NM_005080_1674-1692ACUUCAAGUAAGAUCAAGANN 3581 UCUUGAUCUUACUUGAAGUNN 3582NM_005080_1675-1693 CUUCAAGUAAGAUCAAGAANN 3583 UUCUUGAUCUUACUUGAAGNN3584 NM_005080_330-348 AAUGAGUGAGCUGGAACAGNN 3585 CUGUUCCAGCUCACUCAUUNN3586 NM_005080_333-351 GAGUGAGCUGGAACAGCAANN 3587 UUGCUGUUCCAGCUCACUCNN3588 NM_005080_592-610 CCCCUCCAGAACAUCUCCCNN 3589 GGGAGAUGUUCUGGAGGGGNN3590 NM_005080_665-683 CAUUCUGGACAACUUGGACNN 3591 GUCCAAGUUGUCCAGAAUGNN3592 NM_005080_815-833 GGAAGCCAUUAAUGAACUANN 3593 UAGUUCAUUAAUGGCUUCCNN3594 NM_005080_1029-1047 CUGCUUUCAUCCAGCCACUNN 3595AGUGGCUGGAUGAAAGCAGNN 3596 NM_005080_1077-1095 GCUUACAGUGACUGUGGAUNN3597 AUCCACAGUCACUGUAAGCNN 3598 NM_005080_1222-1240GUUGCCCUUUUCCUUGACUNN 3599 AGUCAAGGAAAAGGGCAACNN 3600NM_005080_1285-1303 UUCAAAAAGCCAAAAUAGANN 3601 UCUAUUUUGGCUUUUUGAANN3602 NM_005080_1334-1352 UGUUCAGAUCUCAUAGAUGNN 3603CAUCUAUGAGAUCUGAACANN 3604 NM_005080_1335-1353 GUUCAGAUCUCAUAGAUGANN3605 UCAUCUAUGAGAUCUGAACNN 3606 NM_005080_1436-1454GAACUACAGCUUUUAAGAUNN 3607 AUCUUAAAAGCUGUAGUUCNN 3608NM_005080_1449-1467 UAAGAUUGUACUUUUAUCUNN 3609 AGAUAAAAGUACAAUCUUANN3610 NM_005080_1450-1468 AAGAUUGUACUUUUAUCUUNN 3611AAGAUAAAAGUACAAUCUUNN 3612 NM_005080_114-132 GCAGCCCGCCUCCGCCGCCNN 3613GGCGGCGGAGGCGGGCUGCNN 3614 NM_005080_1555-1573 UUCUUUAUCAUUUCUCUUCNN3615 GAAGAGAAAUGAUAAAGAANN 3616 NM_005080_1556-1574UCUUUAUCAUUUCUCUUCCNN 3617 GGAAGAGAAAUGAUAAAGANN 3618NM_005080_1561-1579 AUCAUUUCUCUUCCCCCUUNN 3619 AAGGGGGAAGAGAAAUGAUNN3620 NM_005080_1562-1580 UCAUUUCUCUUCCCCCUUUNN 3621AAAGGGGGAAGAGAAAUGANN 3622 NM_005080_1569-1587 UCUUCCCCCUUUUUGGCAUNN3623 AUGCCAAAAAGGGGGAAGANN 3624 NM_005080_1588-1606CCUGGCUUGCCUCCAGUUUNN 3625 AAACUGGAGGCAAGCCAGGNN 3626NM_005080_1640-1658 AACACCUGCUGAGGGGGCUNN 3627 AGCCCCCUCAGCAGGUGUUNN3628 NM_005080_1641-1659 ACACCUGCUGAGGGGGCUCNN 3629GAGCCCCCUCAGCAGGUGUNN 3630 NM_005080_1642-1660 CACCUGCUGAGGGGGCUCUNN3631 AGAGCCCCCUCAGCAGGUGNN 3632 NM_005080_1650-1668GAGGGGGCUCUUUCCCUCANN 3633 UGAGGGAAAGAGCCCCCUCNN 3634NM_005080_1686-1704 AUCAAGAAUCUUUUGUGAANN 3635 UUCACAAAAGAUUCUUGAUNN3636 NM_005080_1745-1763 UCCUGCUAGUGUAGCUUCUNN 3637AGAAGCUACACUAGCAGGANN 3638 NM_005080_138-156 CCCGGCCGGCCAGGCCCUGNN 3639CAGGGCCUGGCCGGCCGGGNN 3640 NM_005080_145-163 GGCCAGGCCCUGCCGCUCANN 3641UGAGCGGCAGGGCCUGGCCNN 3642 NM_005080_190-208 CCGGAGGCAGCGAGCGGGGNN 3643CCCCGCTCGCTGCCTCCGGNN 3644 NM_005080_191-209 CGGAGGCAGCGAGCGGGGGNN 3645CCCCCGCTCGCTGCCTCCGNN 3646 NM_005080_192-210 GGAGGCAGCGAGCGGGGGGNN 3647CCCCCCGCTCGCTGCCTCCNN 3648 NM_005080_259-277 GAGAAGGCGCUGAGGAGGANN 3649UCCUCCUCAGCGCCUUCUCNN 3650 NM_005080_261-279 GAAGGCGCUGAGGAGGAAANN 3651UUUCCUCCUCAGCGCCUUCNN 3652 NM_005080_289-307 AGAGUAGCAGCUCAGACUGNN 3653CAGUCUGAGCUGCUACUCUNN 3654 NM_005080_363-381 AGAAGAAGAGAACCAAAAANN 3655TTTTTGGTTCTCTTCTTCTNN 3656 NM_005080_365-383 AAGAAGAGAACCAAAAACUNN 3657AGUUUUUGGUUCUCUUCUUNN 3658 NM_005080_385-403 UUGCUAGAAAAUCAGCUUUNN 3659AAAGCUGAUUUUCUAGCAANN 3660 NM_005080_461-479 GGAUGGAUGCCCUGGUUGCNN 3661GCAACCAGGGCAUCCAUCCNN 3662 NM_005080_490-508 GCGGAAGCCAAGGGGAAUGNN 3663CAUUCCCCUUGGCUUCCGCNN 3664 NM_005080_518-536 CAGUGGCCGGGUCUGCUGANN 3665UCAGCAGACCCGGCCACUGNN 3666 NM_005080_673-691 ACAACUUGGACCCAGUCAUNN 3667AUGACUGGGUCCAAGUUGUNN 3668 NM_005080_685-703 CAGUCAUGUUCUUCAAAUGNN 3669CAUUUGAAGAACAUGACUGNN 3670 NM_005080_730-748 AGGAGCUCCCAGAGGUCUANN 3671UAGACCUCUGGGAGCUCCUNN 3672 NM_005080_772-790 CAGCCUCCCUUUCUCUGUCNN 3673GACAGAGAAAGGGAGGCUGNN 3674 NM_005080_801-819 UCAUCAGCCAAGCUGGAAGNN 3675CUUCCAGCUUGGCUGAUGANN 3676 NM_005080_817-835 AAGCCAUUAAUGAACUAAUNN 3677AUUAGUUCAUUAAUGGCUUNN 3678 NM_005080_887-905 GACAGAGAGCCAAGCUAAUNN 3679AUUAGCUUGGCUCUCUGUCNN 3680 NM_005080_924-942 GAAGCACCUCUCAGCCCCUNN 3681AGGGGCUGAGAGGUGCUUCNN 3682 NM_005080_927-945 GCACCUCUCAGCCCCUCAGNN 3683CUGAGGGGCUGAGAGGUGCNN 3684 NM_005080_928-946 CACCUCUCAGCCCCUCAGANN 3685UCUGAGGGGCUGAGAGGUGNN 3686 NM_005080_974-992 AGUGAAGGAAGAACCUGUANN 3687UACAGGUUCUUCCUUCACUNN 3688 NM_005080_985-1003 AACCUGUAGAAGAUGACCUNN 3689AGGUCAUCUUCUACAGGUUNN 3690 NM_005080_187-205 AGCCCGGAGGCAGCGAGCGNN 3691CGCTCGCTGCCTCCGGGCTNN 3692 NM_005080_672-690 GACAACUUGGACCCAGUCANN 3693UGACUGGGUCCAAGUUGUCNN 3694 NM_005080_771-789 CCAGCCUCCCUUUCUCUGUNN 3695ACAGAGAAAGGGAGGCUGGNN 3696 NM_005080_1740-1758 UUUUUUCCUGCUAGUGUAGNN3697 CUACACUAGCAGGAAAAAANN 3698 NM_005080_1741-1759UUUUUCCUGCUAGUGUAGCNN 3699 GCUACACUAGCAGGAAAAANN 3700 NM_005080_662-680GGGCAUUCUGGACAACUUGNN 3701 CAAGUUGUCCAGAAUGCCCNN 3702NM_005080_1070-1088 ACUGGAUGCUUACAGUGACNN 3703 GUCACUGUAAGCAUCCAGUNN3704 NM_005080_631-649 ACUCUUCAGAUUCAGAGUCNN 3705 GACUCUGAAUCUGAAGAGUNN3706 NM_005080_647-665 GUCUGAUAUCCUGUUGGGCNN 3707 GCCCAACAGGAUAUCAGACNN3708 NM_005080_791-809 AGUGGGGACGUCAUCAGCCNN 3709 GGCUGAUGACGUCCCCACUNN3710 NM_005080_981-999 GAAGAACCUGUAGAAGAUGNN 3711 CAUCUUCUACAGGUUCUUCNN3712 NM_005080_1068-1086 CUACUGGAUGCUUACAGUGNN 3713CACUGUAAGCAUCCAGUAGNN 3714 NM_005080_1391-1409 GUAUUGAGACAUAUUACUGNN3715 CAGUAAUAUGUCUCAAUACNN 3716 NM_005080_1426-1444CUAUAAUUGAGAACUACAGNN 3717 CUGUAGUUCUCAAUUAUAGNN 3718 NM_005080_103-121CUUCUGUCGGGGCAGCCCGNN 3719 CGGGCUGCCCCGACAGAAGNN 3720NM_005080_1457-1475 UACUUUUAUCUUAAAAGGGNN 3721 CCCUUUUAAGAUAAAAGUANN3722 NM_005080_1568-1586 CUCUUCCCCCUUUUUGGCANN 3723UGCCAAAAAGGGGGAAGAGNN 3724 NM_005080_1574-1592 CCCCUUUUUGGCAUCCUGGNN3725 CCAGGAUGCCAAAAAGGGGNN 3726 NM_005080_1577-1595CUUUUUGGCAUCCUGGCUUNN 3727 AAGCCAGGAUGCCAAAAAGNN 3728NM_005080_1730-1748 CUUGAUGGAAUUUUUUCCUNN 3729 AGGAAAAAAUUCCAUCAAGNN3730 NM_005080_1731-1749 UUGAUGGAAUUUUUUCCUGNN 3731CAGGAAAAAAUUCCAUCAANN 3732 NM_005080_1732-1750 UGAUGGAAUUUUUUCCUGCNN3733 GCAGGAAAAAAUUCCAUCANN 3734 NM_005080_293-311 UAGCAGCUCAGACUGCCAGNN3735 CUGGCAGUCUGAGCUGCUANN 3736 NM_005080_350-368 AAGUGGUAGAUUUAGAAGANN3737 UCUUCUAAAUCUACCACUUNN 3738 NM_005080_351-369 AGUGGUAGAUUUAGAAGAANN3739 UUCUUCUAAAUCUACCACUNN 3740 NM_005080_630-648 GACUCUUCAGAUUCAGAGUNN3741 ACUCUGAAUCUGAAGAGUCNN 3742 NM_005080_657-675 CUGUUGGGCAUUCUGGACANN3743 UGUCCAGAAUGCCCAACAGNN 3744 NM_005080_670-688 UGGACAACUUGGACCCAGUNN3745 ACUGGGUCCAAGUUGUCCANN 3746 NM_005080_692-710 GUUCUUCAAAUGCCCUUCCNN3747 GGAAGGGCAUUUGAAGAACNN 3748 NM_005080_778-796 CCCUUUCUCUGUCAGUGGGNN3749 CCCACUGACAGAGAAAGGGNN 3750 NM_005080_790-808 CAGUGGGGACGUCAUCAGCNN3751 GCUGAUGACGUCCCCACUGNN 3752 NM_005080_970-988 UCUCAGUGAAGGAAGAACCNN3753 GGUUCUUCCUUCACUGAGANN 3754 NM_005080_1162-1180ACACUUUUGCCAAUGAACUNN 3755 AGUUCAUUGGCAAAAGUGUNN 3756NM_005080_1368-1386 CUUUUGACAUCCAGCAGUCNN 3757 GACUGCUGGAUGUCAAAAGNN3758 NM_005080_1515-1533 UAGACAAAUGUCUUGAAGUNN 3759ACUUCAAGACAUUUGUCUANN 3760 NM_005080_1541-1559 GAAUUUAUGAAUGGUUCUUNN3761 AAGAACCAUUCAUAAAUUCNN 3762 NM_005080_1542-1560AAUUUAUGAAUGGUUCUUUNN 3763 AAAGAACCAUUCAUAAAUUNN 3764NM_005080_1571-1589 UUCCCCCUUUUUGGCAUCCNN 3765 GGAUGCCAAAAAGGGGGAANN3766 NM_005080_151-169 GCCCUGCCGCUCAUGGUGCNN 3767 GCACCAUGAGCGGCAGGGCNN3768 NM_005080_160-178 CUCAUGGUGCCAGCCCAGANN 3769 UCUGGGCUGGCACCAUGAGNN3770 NM_005080_326-344 CUCGAAUGAGUGAGCUGGANN 3771 UCCAGCUCACUCAUUCGAGNN3772 NM_005080_327-345 UCGAAUGAGUGAGCUGGAANN 3773 UUCCAGCUCACUCAUUCGANN3774 NM_005080_331-349 AUGAGUGAGCUGGAACAGCNN 3775 GCUGUUCCAGCUCACUCAUNN3776 NM_005080_424-442 CUUGUAGUUGAGAACCAGGNN 3777 CCUGGUUCUCAACUACAAGNN3778 NM_005080_483-501 AGAGGAGGCGGAAGCCAAGNN 3779 CTTGGCTTCCGCCTCCTCTNN3780 NM_005080_579-597 GGCCCAGUUGUCACCCCUCNN 3781 GAGGGGUGACAACUGGGCCNN3782 NM_005080_745-763 UCUACCCAGAAGGACCCAGNN 3783 CUGGGUCCUUCUGGGUAGANN3784 NM_005080_746-764 CUACCCAGAAGGACCCAGUNN 3785 ACUGGGUCCUUCUGGGUAGNN3786 NM_005080_812-830 GCUGGAAGCCAUUAAUGAANN 3787 UUCAUUAAUGGCUUCCAGCNN3788 NM_005080_871-889 UAGAGAUACCCUCUGAGACNN 3789 GUCUCAGAGGGUAUCUCUANN3790 NM_005080_892-910 AGAGCCAAGCUAAUGUGGUNN 3791 ACCACAUUAGCUUGGCUCUNN3792 NM_005080_978-996 AAGGAAGAACCUGUAGAAGNN 3793 CUUCUACAGGUUCUUCCUUNN3794 NM_005080_982-1000 AAGAACCUGUAGAAGAUGANN 3795 UCAUCUUCUACAGGUUCUUNN3796 NM_005080_257-275 AGGAGAAGGCGCUGAGGAGNN 3797 CUCCUCAGCGCCUUCUCCUNN3798 NM_005080_364-382 GAAGAAGAGAACCAAAAACNN 3799 GTTTTTGGTTCTCTTCTTCNN3800 NM_005080_816-834 GAAGCCAUUAAUGAACUAANN 3801 UUAGUUCAUUAAUGGCUUCNN3802 NM_005080_884-902 UGAGACAGAGAGCCAAGCUNN 3803 AGCUUGGCUCUCUGUCUCANN3804 NM_005080_925-943 AAGCACCUCUCAGCCCCUCNN 3805 GAGGGGCUGAGAGGUGCUUNN3806 NM_005080_1440-1458 UACAGCUUUUAAGAUUGUANN 3807UACAAUCUUAAAAGCUGUANN 3808 NM_005080_784-802 CUCUGUCAGUGGGGACGUCNN 3809GACGUCCCCACUGACAGAGNN 3810 NM_005080_1593-1611 CUUGCCUCCAGUUUUAGGUNN3811 ACCUAAAACUGGAGGCAAGNN 3812 NM_005080_301-319 CAGACUGCCAGAGAUCGAANN3813 UUCGAUCUCUGGCAGUCUGNN 3814 NM_005080_674-692 CAACUUGGACCCAGUCAUGNN3815 CAUGACUGGGUCCAAGUUGNN 3816 NM_005080_783-801 UCUCUGUCAGUGGGGACGUNN3817 ACGUCCCCACUGACAGAGANN 3818 NM_005080_921-939 GAGGAAGCACCUCUCAGCCNN3819 GGCUGAGAGGUGCUUCCUCNN 3820 NM_005080_1226-1244CCCUUUUCCUUGACUAUUANN 3821 UAAUAGUCAAGGAAAAGGGNN 3822NM_005080_1283-1301 CAUUCAAAAAGCCAAAAUANN 3823 UAUUUUGGCUUUUUGAAUGNN3824 NM_005080_1416-1434 AGAAAUAUUACUAUAAUUGNN 3825CAAUUAUAGUAAUAUUUCUNN 3826 NM_005080_1420-1438 AUAUUACUAUAAUUGAGAANN3827 UUCUCAAUUAUAGUAAUAUNN 3828 NM_005080_1488-1506CUAAAAUACUUAUUAUGUANN 3829 UACAUAAUAAGUAUUUUAGNN 3830NM_005080_1492-1510 AAUACUUAUUAUGUAAGGGNN 3831 CCCUUACAUAAUAAGUAUUNN3832 NM_005080_111-129 GGGGCAGCCCGCCUCCGCCNN 3833 GGCGGAGGCGGGCUGCCCCNN3834 NM_005080_1639-1657 GAACACCUGCUGAGGGGGCNN 3835GCCCCCUCAGCAGGUGUUCNN 3836 NM_005080_1685-1703 GAUCAAGAAUCUUUUGUGANN3837 UCACAAAAGAUUCUUGAUCNN 3838 NM_005080_1733-1751GAUGGAAUUUUUUCCUGCUNN 3839 AGCAGGAAAAAAUUCCAUCNN 3840NM_005080_1734-1752 AUGGAAUUUUUUCCUGCUANN 3841 UAGCAGGAAAAAAUUCCAUNN3842 NM_005080_1737-1755 GAAUUUUUUCCUGCUAGUGNN 3843CACUAGCAGGAAAAAAUUCNN 3844 NM_005080_1756-1774 UAGCUUCUGAAAGGUGCUUNN3845 AAGCACCUUUCAGAAGCUANN 3846 NM_005080_1757-1775AGCUUCUGAAAGGUGCUUUNN 3847 AAAGCACCUUUCAGAAGCUNN 3848 NM_005080_152-170CCCUGCCGCUCAUGGUGCCNN 3849 GGCACCAUGAGCGGCAGGGNN 3850 NM_005080_153-171CCUGCCGCUCAUGGUGCCANN 3851 UGGCACCAUGAGCGGCAGGNN 3852 NM_005080_163-181AUGGUGCCAGCCCAGAGAGNN 3853 CUCUCUGGGCUGGCACCAUNN 3854 NM_005080_167-185UGCCAGCCCAGAGAGGGGCNN 3855 GCCCCUCUCUGGGCUGGCANN 3856 NM_005080_200-218CGAGCGGGGGGCUGCCCCANN 3857 UGGGGCAGCCCCCCGCUCGNN 3858 NM_005080_252-270CCCCGAGGAGAAGGCGCUGNN 3859 CAGCGCCUUCUCCUCGGGGNN 3860 NM_005080_255-273CGAGGAGAAGGCGCUGAGGNN 3861 CCUCAGCGCCUUCUCCUCGNN 3862 NM_005080_260-278AGAAGGCGCUGAGGAGGAANN 3863 UUCCUCCUCAGCGCCUUCUNN 3864 NM_005080_271-289AGGAGGAAACUGAAAAACANN 3865 UGUUUUUCAGUUUCCUCCUNN 3866 NM_005080_297-315AGCUCAGACUGCCAGAGAUNN 3867 AUCUCUGGCAGUCUGAGCUNN 3868 NM_005080_300-318UCAGACUGCCAGAGAUCGANN 3869 UCGAUCUCUGGCAGUCUGANN 3870 NM_005080_335-353GUGAGCUGGAACAGCAAGUNN 3871 ACUUGCUGUUCCAGCUCACNN 3872 NM_005080_368-386AAGAGAACCAAAAACUUUUNN 3873 AAAAGUUUUUGGUUCUCUUNN 3874 NM_005080_378-396AAAACUUUUGCUAGAAAAUNN 3875 AUUUUCUAGCAAAAGUUUUNN 3876 NM_005080_379-397AAACUUUUGCUAGAAAAUCNN 3877 GAUUUUCUAGCAAAAGUUUNN 3878 NM_005080_380-398AACUUUUGCUAGAAAAUCANN 3879 UGAUUUUCUAGCAAAAGUUNN 3880 NM_005080_389-407UAGAAAAUCAGCUUUUACGNN 3881 CGUAAAAGCUGAUUUUCUANN 3882 NM_005080_426-444UGUAGUUGAGAACCAGGAGNN 3883 CUCCUGGUUCUCAACUACANN 3884 NM_005080_427-445GUAGUUGAGAACCAGGAGUNN 3885 ACUCCUGGUUCUCAACUACNN 3886 NM_005080_485-503AGGAGGCGGAAGCCAAGGGNN 3887 CCCTTGGCTTCCGCCTCCTNN 3888 NM_005080_487-505GAGGCGGAAGCCAAGGGGANN 3889 TCCCCTTGGCTTCCGCCTCNN 3890 NM_005080_488-506AGGCGGAAGCCAAGGGGAANN 3891 TTCCCCTTGGCTTCCGCCTNN 3892 NM_005080_511-529GUGAGGCCAGUGGCCGGGUNN 3893 ACCCGGCCACUGGCCUCACNN 3894 NM_005080_526-544GGGUCUGCUGAGUCCGCAGNN 3895 CUGCGGACUCAGCAGACCCNN 3896 NM_005080_575-593UGCAGGCCCAGUUGUCACCNN 3897 GGUGACAACUGGGCCUGCANN 3898 NM_005080_593-611CCCUCCAGAACAUCUCCCCNN 3899 GGGGAGAUGUUCUGGAGGGNN 3900 NM_005080_595-613CUCCAGAACAUCUCCCCAUNN 3901 AUGGGGAGAUGUUCUGGAGNN 3902 NM_005080_654-672AUCCUGUUGGGCAUUCUGGNN 3903 CCAGAAUGCCCAACAGGAUNN 3904 NM_005080_675-693AACUUGGACCCAGUCAUGUNN 3905 ACAUGACUGGGUCCAAGUUNN 3906 NM_005080_683-701CCCAGUCAUGUUCUUCAAANN 3907 UUUGAAGAACAUGACUGGGNN 3908 NM_005080_684-702CCAGUCAUGUUCUUCAAAUNN 3909 AUUUGAAGAACAUGACUGGNN 3910 NM_005080_693-711UUCUUCAAAUGCCCUUCCCNN 3911 GGGAAGGGCAUUUGAAGAANN 3912 NM_005080_694-712UCUUCAAAUGCCCUUCCCCNN 3913 GGGGAAGGGCAUUUGAAGANN 3914 NM_005080_726-744CUGGAGGAGCUCCCAGAGGNN 3915 CCUCUGGGAGCUCCUCCAGNN 3916 NM_005080_744-762GUCUACCCAGAAGGACCCANN 3917 UGGGUCCUUCUGGGUAGACNN 3918 NM_005080_765-783UCCUUACCAGCCUCCCUUUNN 3919 AAAGGGAGGCUGGUAAGGANN 3920 NM_005080_768-786UUACCAGCCUCCCUUUCUCNN 3921 GAGAAAGGGAGGCUGGUAANN 3922 NM_005080_777-795UCCCUUUCUCUGUCAGUGGNN 3923 CCACUGACAGAGAAAGGGANN 3924 NM_005080_802-820CAUCAGCCAAGCUGGAAGCNN 3925 GCUUCCAGCUUGGCUGAUGNN 3926 NM_005080_877-895UACCCUCUGAGACAGAGAGNN 3927 CUCUCUGUCUCAGAGGGUANN 3928 NM_005080_878-896ACCCUCUGAGACAGAGAGCNN 3929 GCUCUCUGUCUCAGAGGGUNN 3930 NM_005080_885-903GAGACAGAGAGCCAAGCUANN 3931 UAGCUUGGCUCUCUGUCUCNN 3932 NM_005080_886-904AGACAGAGAGCCAAGCUAANN 3933 UUAGCUUGGCUCUCUGUCUNN 3934 NM_005080_966-984AUUGUCUCAGUGAAGGAAGNN 3935 CUUCCUUCACUGAGACAAUNN 3936 NM_005080_969-987GUCUCAGUGAAGGAAGAACNN 3937 GUUCUUCCUUCACUGAGACNN 3938NM_005080_1245-1263 CACUGCCUGGAGGAUAGCANN 3939 UGCUAUCCUCCAGGCAGUGNN3940 NM_005080_1738-1756 AAUUUUUUCCUGCUAGUGUNN 3941ACACUAGCAGGAAAAAAUUNN 3942 NM_005080_194-212 AGGCAGCGAGCGGGGGGCUNN 3943AGCCCCCCGCUCGCUGCCUNN 3944 NM_005080_209-227 GGCUGCCCCAGGCGCGCAANN 3945UUGCGCGCCUGGGGCAGCCNN 3946 NM_005080_269-287 UGAGGAGGAAACUGAAAAANN 3947UUUUUCAGUUUCCUCCUCANN 3948 NM_005080_902-920 UAAUGUGGUAGUGAAAAUCNN 3949GAUUUUCACUACCACAUUANN 3950 NM_005080_50-68 UGGUGGUGGUGGCAGCCGCNN 3951GCGGCUGCCACCACCACCANN 3952 NM_005080_1017-1035 GGUAUCUCAAAUCUGCUUUNN3953 AAAGCAGAUUUGAGAUACCNN 3954 NM_005080_1021-1039UCUCAAAUCUGCUUUCAUCNN 3955 GAUGAAAGCAGAUUUGAGANN 3956NM_005080_1022-1040 CUCAAAUCUGCUUUCAUCCNN 3957 GGAUGAAAGCAGAUUUGAGNN3958 NM_005080_1062-1080 UCCUGCCUACUGGAUGCUUNN 3959AAGCAUCCAGUAGGCAGGANN 3960 NM_005080_1074-1092 GAUGCUUACAGUGACUGUGNN3961 CACAGUCACUGUAAGCAUCNN 3962 NM_005080_1116-1134UUCAGUGACAUGUCCUCUCNN 3963 GAGAGGACAUGUCACUGAANN 3964NM_005080_1149-1167 CAUUCUUGGGAGGACACUUNN 3965 AAGUGUCCUCCCAAGAAUGNN3966 NM_005080_1150-1168 AUUCUUGGGAGGACACUUUNN 3967AAAGUGUCCUCCCAAGAAUNN 3968 NM_005080_1161-1179 GACACUUUUGCCAAUGAACNN3969 GUUCAUUGGCAAAAGUGUCNN 3970 NM_005080_1223-1241UUGCCCUUUUCCUUGACUANN 3971 UAGUCAAGGAAAAGGGCAANN 3972NM_005080_1280-1298 CUUCAUUCAAAAAGCCAAANN 3973 UUUGGCUUUUUGAAUGAAGNN3974 NM_005080_1281-1299 UUCAUUCAAAAAGCCAAAANN 3975UUUUGGCUUUUUGAAUGAANN 3976 NM_005080_1284-1302 AUUCAAAAAGCCAAAAUAGNN3977 CUAUUUUGGCUUUUUGAAUNN 3978 NM_005080_1286-1304UCAAAAAGCCAAAAUAGAGNN 3979 CUCUAUUUUGGCUUUUUGANN 3980NM_005080_1288-1306 AAAAAGCCAAAAUAGAGAGNN 3981 CUCUCUAUUUUGGCUUUUUNN3982 NM_005080_1365-1383 UGUCUUUUGACAUCCAGCANN 3983UGCUGGAUGUCAAAAGACANN 3984 NM_005080_1417-1435 GAAAUAUUACUAUAAUUGANN3985 UCAAUUAUAGUAAUAUUUCNN 3986 NM_005080_1421-1439UAUUACUAUAAUUGAGAACNN 3987 GUUCUCAAUUAUAGUAAUANN 3988NM_005080_1434-1452 GAGAACUACAGCUUUUAAGNN 3989 CUUAAAAGCUGUAGUUCUCNN3990 NM_005080_1452-1470 GAUUGUACUUUUAUCUUAANN 3991UUAAGAUAAAAGUACAAUCNN 3992 NM_005080_105-123 UCUGUCGGGGCAGCCCGCCNN 3993GGCGGGCUGCCCCGACAGANN 3994 NM_005080_1455-1473 UGUACUUUUAUCUUAAAAGNN3995 CUUUUAAGAUAAAAGUACANN 3996 NM_005080_112-130 GGGCAGCCCGCCUCCGCCGNN3997 CGGCGGAGGCGGGCUGCCCNN 3998 NM_005080_113-131 GGCAGCCCGCCUCCGCCGCNN3999 GCGGCGGAGGCGGGCUGCCNN 4000 NM_005080_1543-1561AUUUAUGAAUGGUUCUUUANN 4001 UAAAGAACCAUUCAUAAAUNN 4002NM_005080_1544-1562 UUUAUGAAUGGUUCUUUAUNN 4003 AUAAAGAACCAUUCAUAAANN4004 NM_005080_1557-1575 CUUUAUCAUUUCUCUUCCCNN 4005GGGAAGAGAAAUGAUAAAGNN 4006 NM_005080_115-133 CAGCCCGCCUCCGCCGCCGNN 4007CGGCGGCGGAGGCGGGCUGNN 4008 NM_005080_1564-1582 AUUUCUCUUCCCCCUUUUUNN4009 AAAAAGGGGGAAGAGAAAUNN 4010 NM_005080_1572-1590UCCCCCUUUUUGGCAUCCUNN 4011 AGGAUGCCAAAAAGGGGGANN 4012NM_005080_1575-1593 CCCUUUUUGGCAUCCUGGCNN 4013 GCCAGGAUGCCAAAAAGGGNN4014 NM_005080_1576-1594 CCUUUUUGGCAUCCUGGCUNN 4015AGCCAGGAUGCCAAAAAGGNN 4016 NM_005080_117-135 GCCCGCCUCCGCCGCCGGANN 4017UCCGGCGGCGGAGGCGGGCNN 4018 NM_005080_1582-1600 UGGCAUCCUGGCUUGCCUCNN4019 GAGGCAAGCCAGGAUGCCANN 4020 NM_005080_1587-1605UCCUGGCUUGCCUCCAGUUNN 4021 AACUGGAGGCAAGCCAGGANN 4022 NM_005080_118-136CCCGCCUCCGCCGCCGGAGNN 4023 CUCCGGCGGCGGAGGCGGGNN 4024 NM_005080_119-137CCGCCUCCGCCGCCGGAGCNN 4025 GCUCCGGCGGCGGAGGCGGNN 4026 NM_005080_120-138CGCCUCCGCCGCCGGAGCCNN 4027 GGCUCCGGCGGCGGAGGCGNN 4028 NM_005080_124-142UCCGCCGCCGGAGCCCCGGNN 4029 CCGGGGCUCCGGCGGCGGANN 4030 NM_005080_126-144CGCCGCCGGAGCCCCGGCCNN 4031 GGCCGGGGCTCCGGCGGCGNN 4032NM_005080_1676-1694 UUCAAGUAAGAUCAAGAAUNN 4033 AUUCUUGAUCUUACUUGAANN4034 NM_005080_127-145 GCCGCCGGAGCCCCGGCCGNN 4035 CGGCCGGGGCTCCGGCGGCNN4036 NM_005080_129-147 CGCCGGAGCCCCGGCCGGCNN 4037 GCCGGCCGGGGCTCCGGCGNN4038 NM_005080_130-148 GCCGGAGCCCCGGCCGGCCNN 4039 GGCCGGCCGGGGCTCCGGCNN4040 NM_005080_131-149 CCGGAGCCCCGGCCGGCCANN 4041 TGGCCGGCCGGGGCTCCGGNN4042 NM_005080_1720-1738 UAUGUAAAUGCUUGAUGGANN 4043UCCAUCAAGCAUUUACAUANN 4044 NM_005080_1724-1742 UAAAUGCUUGAUGGAAUUUNN4045 AAAUUCCAUCAAGCAUUUANN 4046 NM_005080_132-150 CGGAGCCCCGGCCGGCCAGNN4047 CTGGCCGGCCGGGGCTCCGNN 4048 NM_005080_133-151 GGAGCCCCGGCCGGCCAGGNN4049 CCTGGCCGGCCGGGGCTCCNN 4050 NM_005080_134-152 GAGCCCCGGCCGGCCAGGCNN4051 GCCTGGCCGGCCGGGGCTCNN 4052 NM_005080_136-154 GCCCCGGCCGGCCAGGCCCNN4053 GGGCCTGGCCGGCCGGGGCNN 4054 NM_005080_1777-1795UCCAUUUAUUUAAAACUACNN 4055 GUAGUUUUAAAUAAAUGGANN 4056 NM_005080_137-155CCCCGGCCGGCCAGGCCCUNN 4057 AGGGCCUGGCCGGCCGGGGNN 4058 NM_005080_139-157CCGGCCGGCCAGGCCCUGCNN 4059 GCAGGGCCUGGCCGGCCGGNN 4060 NM_005080_140-158CGGCCGGCCAGGCCCUGCCNN 4061 GGCAGGGCCUGGCCGGCCGNN 4062 NM_005080_141-159GGCCGGCCAGGCCCUGCCGNN 4063 CGGCAGGGCCUGGCCGGCCNN 4064 NM_005080_142-160GCCGGCCAGGCCCUGCCGCNN 4065 GCGGCAGGGCCUGGCCGGCNN 4066 NM_005080_143-161CCGGCCAGGCCCUGCCGCUNN 4067 AGCGGCAGGGCCUGGCCGGNN 4068 NM_005080_144-162CGGCCAGGCCCUGCCGCUCNN 4069 GAGCGGCAGGGCCUGGCCGNN 4070 NM_005080_161-179UCAUGGUGCCAGCCCAGAGNN 4071 CUCUGGGCUGGCACCAUGANN 4072 NM_005080_162-180CAUGGUGCCAGCCCAGAGANN 4073 UCUCUGGGCUGGCACCAUGNN 4074 NM_005080_164-182UGGUGCCAGCCCAGAGAGGNN 4075 CCUCUCUGGGCUGGCACCANN 4076 NM_005080_165-183GGUGCCAGCCCAGAGAGGGNN 4077 CCCUCUCUGGGCUGGCACCNN 4078 NM_005080_166-184GUGCCAGCCCAGAGAGGGGNN 4079 CCCCUCUCUGGGCUGGCACNN 4080 NM_005080_201-219GAGCGGGGGGCUGCCCCAGNN 4081 CUGGGGCAGCCCCCCGCUCNN 4082 NM_005080_202-220AGCGGGGGGCUGCCCCAGGNN 4083 CCUGGGGCAGCCCCCCGCUNN 4084 NM_005080_203-221GCGGGGGGCUGCCCCAGGCNN 4085 GCCUGGGGCAGCCCCCCGCNN 4086 NM_005080_204-222CGGGGGGCUGCCCCAGGCGNN 4087 CGCCUGGGGCAGCCCCCCGNN 4088 NM_005080_208-226GGGCUGCCCCAGGCGCGCANN 4089 UGCGCGCCUGGGGCAGCCCNN 4090 NM_005080_212-230UGCCCCAGGCGCGCAAGCGNN 4091 CGCUUGCGCGCCUGGGGCANN 4092 NM_005080_248-266UGAGCCCCGAGGAGAAGGCNN 4093 GCCUUCUCCUCGGGGCUCANN 4094 NM_005080_251-269GCCCCGAGGAGAAGGCGCUNN 4095 AGCGCCUUCUCCUCGGGGCNN 4096 NM_005080_258-276GGAGAAGGCGCUGAGGAGGNN 4097 CCUCCUCAGCGCCUUCUCCNN 4098 NM_005080_262-280AAGGCGCUGAGGAGGAAACNN 4099 GUUUCCUCCUCAGCGCCUUNN 4100 NM_005080_265-283GCGCUGAGGAGGAAACUGANN 4101 UCAGUUUCCUCCUCAGCGCNN 4102 NM_005080_266-284CGCUGAGGAGGAAACUGAANN 4103 UUCAGUUUCCUCCUCAGCGNN 4104 NM_005080_267-285GCUGAGGAGGAAACUGAAANN 4105 UUUCAGUUUCCUCCUCAGCNN 4106 NM_005080_268-286CUGAGGAGGAAACUGAAAANN 4107 UUUUCAGUUUCCUCCUCAGNN 4108 NM_005080_270-288GAGGAGGAAACUGAAAAACNN 4109 GUUUUUCAGUUUCCUCCUCNN 4110 NM_005080_272-290GGAGGAAACUGAAAAACAGNN 4111 CUGUUUUUCAGUUUCCUCCNN 4112 NM_005080_273-291GAGGAAACUGAAAAACAGANN 4113 UCUGUUUUUCAGUUUCCUCNN 4114 NM_005080_277-295AAACUGAAAAACAGAGUAGNN 4115 CUACUCUGUUUUUCAGUUUNN 4116 NM_005080_328-346CGAAUGAGUGAGCUGGAACNN 4117 GUUCCAGCUCACUCAUUCGNN 4118 NM_005080_329-347GAAUGAGUGAGCUGGAACANN 4119 UGUUCCAGCUCACUCAUUCNN 4120 NM_005080_334-352AGUGAGCUGGAACAGCAAGNN 4121 CUUGCUGUUCCAGCUCACUNN 4122 NM_005080_336-354UGAGCUGGAACAGCAAGUGNN 4123 CACUUGCUGUUCCAGCUCANN 4124 NM_005080_337-355GAGCUGGAACAGCAAGUGGNN 4125 CCACUUGCUGUUCCAGCUCNN 4126 NM_005080_338-356AGCUGGAACAGCAAGUGGUNN 4127 ACCACUUGCUGUUCCAGCUNN 4128 NM_005080_356-374UAGAUUUAGAAGAAGAGAANN 4129 UUCUCUUCUUCUAAAUCUANN 4130 NM_005080_357-375AGAUUUAGAAGAAGAGAACNN 4131 GUUCUCUUCUUCUAAAUCUNN 4132 NM_005080_359-377AUUUAGAAGAAGAGAACCANN 4133 UGGUUCUCUUCUUCUAAAUNN 4134 NM_005080_360-378UUUAGAAGAAGAGAACCAANN 4135 UUGGUUCUCUUCUUCUAAANN 4136 NM_005080_362-380UAGAAGAAGAGAACCAAAANN 4137 UUUUGGUUCUCUUCUUCUANN 4138 NM_005080_367-385GAAGAGAACCAAAAACUUUNN 4139 AAAGUUUUUGGUUCUCUUCNN 4140 NM_005080_382-400CUUUUGCUAGAAAAUCAGCNN 4141 GCUGAUUUUCUAGCAAAAGNN 4142 NM_005080_386-404UGCUAGAAAAUCAGCUUUUNN 4143 AAAAGCUGAUUUUCUAGCANN 4144 NM_005080_401-419UUUUACGAGAGAAAACUCANN 4145 UGAGUUUUCUCUCGUAAAANN 4146 NM_005080_458-476UGGGGAUGGAUGCCCUGGUNN 4147 ACCAGGGCAUCCAUCCCCANN 4148 NM_005080_484-502GAGGAGGCGGAAGCCAAGGNN 4149 CCTTGGCTTCCGCCTCCTCNN 4150 NM_005080_489-507GGCGGAAGCCAAGGGGAAUNN 4151 AUUCCCCUUGGCUUCCGCCNN 4152 NM_005080_574-592GUGCAGGCCCAGUUGUCACNN 4153 GUGACAACUGGGCCUGCACNN 4154 NM_005080_594-612CCUCCAGAACAUCUCCCCANN 4155 UGGGGAGAUGUUCUGGAGGNN 4156 NM_005080_604-622AUCUCCCCAUGGAUUCUGGNN 4157 CCAGAAUCCAUGGGGAGAUNN 4158 NM_005080_627-645AUUGACUCUUCAGAUUCAGNN 4159 CUGAAUCUGAAGAGUCAAUNN 4160 NM_005080_635-653UUCAGAUUCAGAGUCUGAUNN 4161 AUCAGACUCUGAAUCUGAANN 4162 NM_005080_636-654UCAGAUUCAGAGUCUGAUANN 4163 UAUCAGACUCUGAAUCUGANN 4164 NM_005080_666-684AUUCUGGACAACUUGGACCNN 4165 GGUCCAAGUUGUCCAGAAUNN 4166 NM_005080_667-685UUCUGGACAACUUGGACCCNN 4167 GGGUCCAAGUUGUCCAGAANN 4168 NM_005080_669-687CUGGACAACUUGGACCCAGNN 4169 CUGGGUCCAAGUUGUCCAGNN 4170 NM_005080_681-699GACCCAGUCAUGUUCUUCANN 4171 UGAAGAACAUGACUGGGUCNN 4172 NM_005080_690-708AUGUUCUUCAAAUGCCCUUNN 4173 AAGGGCAUUUGAAGAACAUNN 4174 NM_005080_718-736CUGCCAGCCUGGAGGAGCUNN 4175 AGCUCCUCCAGGCUGGCAGNN 4176 NM_005080_722-740CAGCCUGGAGGAGCUCCCANN 4177 UGGGAGCUCCUCCAGGCUGNN 4178 NM_005080_723-741AGCCUGGAGGAGCUCCCAGNN 4179 CUGGGAGCUCCUCCAGGCUNN 4180 NM_005080_724-742GCCUGGAGGAGCUCCCAGANN 4181 UCUGGGAGCUCCUCCAGGCNN 4182 NM_005080_725-743CCUGGAGGAGCUCCCAGAGNN 4183 CUCUGGGAGCUCCUCCAGGNN 4184 NM_005080_727-745UGGAGGAGCUCCCAGAGGUNN 4185 ACCUCUGGGAGCUCCUCCANN 4186 NM_005080_728-746GGAGGAGCUCCCAGAGGUCNN 4187 GACCUCUGGGAGCUCCUCCNN 4188 NM_005080_739-757CAGAGGUCUACCCAGAAGGNN 4189 CCUUCUGGGUAGACCUCUGNN 4190 NM_005080_747-765UACCCAGAAGGACCCAGUUNN 4191 AACUGGGUCCUUCUGGGUANN 4192 NM_005080_763-781GUUCCUUACCAGCCUCCCUNN 4193 AGGGAGGCUGGUAAGGAACNN 4194 NM_005080_764-782UUCCUUACCAGCCUCCCUUNN 4195 AAGGGAGGCUGGUAAGGAANN 4196 NM_005080_766-784CCUUACCAGCCUCCCUUUCNN 4197 GAAAGGGAGGCUGGUAAGGNN 4198 NM_005080_770-788ACCAGCCUCCCUUUCUCUGNN 4199 CAGAGAAAGGGAGGCUGGUNN 4200 NM_005080_774-792GCCUCCCUUUCUCUGUCAGNN 4201 CUGACAGAGAAAGGGAGGCNN 4202 NM_005080_780-798CUUUCUCUGUCAGUGGGGANN 4203 UCCCCACUGACAGAGAAAGNN 4204 NM_005080_781-799UUUCUCUGUCAGUGGGGACNN 4205 GUCCCCACUGACAGAGAAANN 4206 NM_005080_805-823CAGCCAAGCUGGAAGCCAUNN 4207 AUGGCUUCCAGCUUGGCUGNN 4208 NM_005080_44-62GAGCUAUGGUGGUGGUGGCNN 4209 GCCACCACCACCAUAGCUCNN 4210 NM_005080_45-63AGCUAUGGUGGUGGUGGCANN 4211 UGCCACCACCACCAUAGCUNN 4212 NM_005080_868-886UCUUAGAGAUACCCUCUGANN 4213 UCAGAGGGUAUCUCUAAGANN 4214 NM_005080_875-893GAUACCCUCUGAGACAGAGNN 4215 CUCUGUCUCAGAGGGUAUCNN 4216 NM_005080_47-65CUAUGGUGGUGGUGGCAGCNN 4217 GCUGCCACCACCACCAUAGNN 4218 NM_005080_879-897CCCUCUGAGACAGAGAGCCNN 4219 GGCUCUCUGUCUCAGAGGGNN 4220 NM_005080_880-898CCUCUGAGACAGAGAGCCANN 4221 UGGCUCUCUGUCUCAGAGGNN 4222 NM_005080_881-899CUCUGAGACAGAGAGCCAANN 4223 UUGGCUCUCUGUCUCAGAGNN 4224 NM_005080_882-900UCUGAGACAGAGAGCCAAGNN 4225 CUUGGCUCUCUGUCUCAGANN 4226 NM_005080_883-901CUGAGACAGAGAGCCAAGCNN 4227 GCUUGGCUCUCUGUCUCAGNN 4228 NM_005080_49-67AUGGUGGUGGUGGCAGCCGNN 4229 CGGCUGCCACCACCACCAUNN 4230 NM_005080_914-932GAAAAUCGAGGAAGCACCUNN 4231 AGGUGCUUCCUCGAUUUUCNN 4232 NM_005080_915-933AAAAUCGAGGAAGCACCUCNN 4233 GAGGUGCUUCCUCGAUUUUNN 4234 NM_005080_926-944AGCACCUCUCAGCCCCUCANN 4235 UGAGGGGCUGAGAGGUGCUNN 4236 NM_005080_945-963GAGAAUGAUCACCCUGAAUNN 4237 AUUCAGGGUGAUCAUUCUCNN 4238 NM_005080_958-976CUGAAUUCAUUGUCUCAGUNN 4239 ACUGAGACAAUGAAUUCAGNN 4240 NM_005080_959-977UGAAUUCAUUGUCUCAGUGNN 4241 CACUGAGACAAUGAAUUCANN 4242 NM_005080_962-980AUUCAUUGUCUCAGUGAAGNN 4243 CUUCACUGAGACAAUGAAUNN 4244 NM_005080_975-993GUGAAGGAAGAACCUGUAGNN 4245 CUACAGGUUCUUCCUUCACNN 4246 NM_005080_983-1001AGAACCUGUAGAAGAUGACNN 4247 GUCAUCUUCUACAGGUUCUNN 4248 NM_005080_128-146CCGCCGGAGCCCCGGCCGGNN 4249 CCGGCCGGGGCTCCGGCGGNN 4250 NM_005080_249-267GAGCCCCGAGGAGAAGGCGNN 4251 CGCCTTCTCCTCGGGGCTCNN 4252 NM_005080_697-715UCAAAUGCCCUUCCCCAGANN 4253 UCUGGGGAAGGGCAUUUGANN 4254 NM_005080_729-747GAGGAGCUCCCAGAGGUCUNN 4255 AGACCUCUGGGAGCUCCUCNN 4256 NM_005080_776-794CUCCCUUUCUCUGUCAGUGNN 4257 CACUGACAGAGAAAGGGAGNN 4258 NM_005080_803-821AUCAGCCAAGCUGGAAGCCNN 4259 GGCUUCCAGCUUGGCUGAUNN 4260 NM_005080_254-272CCGAGGAGAAGGCGCUGAGNN 4261 CUCAGCGCCUUCUCCUCGGNN 4262 NM_005080_383-401UUUUGCUAGAAAAUCAGCUNN 4263 AGCUGAUUUUCUAGCAAAANN 4264 NM_005080_116-134AGCCCGCCUCCGCCGCCGGNN 4265 CCGGCGGCGGAGGCGGGCUNN 4266 NM_005080_123-141CUCCGCCGCCGGAGCCCCGNN 4267 CGGGGCUCCGGCGGCGGAGNN 4268 NM_005080_125-143CCGCCGCCGGAGCCCCGGCNN 4269 GCCGGGGCTCCGGCGGCGGNN 4270 NM_005080_135-153AGCCCCGGCCGGCCAGGCCNN 4271 GGCCTGGCCGGCCGGGGCTNN 4272 NM_005080_253-271CCCGAGGAGAAGGCGCUGANN 4273 UCAGCGCCUUCUCCUCGGGNN 4274 NM_005080_274-292AGGAAACUGAAAAACAGAGNN 4275 CUCUGUUUUUCAGUUUCCUNN 4276 NM_005080_655-673UCCUGUUGGGCAUUCUGGANN 4277 UCCAGAAUGCCCAACAGGANN 4278 NM_005080_775-793CCUCCCUUUCUCUGUCAGUNN 4279 ACUGACAGAGAAAGGGAGGNN 4280 NM_005080_46-64GCUAUGGUGGUGGUGGCAGNN 4281 CUGCCACCACCACCAUAGCNN 4282NM_005080_1456-1474 GUACUUUUAUCUUAAAAGGNN 4283 CCUUUUAAGAUAAAAGUACNN4284 NM_005080_1545-1563 UUAUGAAUGGUUCUUUAUCNN 4285GAUAAAGAACCAUUCAUAANN 4286 NM_005080_1558-1576 UUUAUCAUUUCUCUUCCCCNN4287 GGGGAAGAGAAAUGAUAAANN 4288 NM_005080_121-139 GCCUCCGCCGCCGGAGCCCNN4289 GGGCUCCGGCGGCGGAGGCNN 4290 NM_005080_122-140 CCUCCGCCGCCGGAGCCCCNN4291 GGGGCUCCGGCGGCGGAGGNN 4292 NM_005080_247-265 CUGAGCCCCGAGGAGAAGGNN4293 CCUUCUCCUCGGGGCUCAGNN 4294 NM_005080_275-293 GGAAACUGAAAAACAGAGUNN4295 ACUCUGUUUUUCAGUUUCCNN 4296 NM_005080_276-294 GAAACUGAAAAACAGAGUANN4297 UACUCUGUUUUUCAGUUUCNN 4298 NM_005080_358-376 GAUUUAGAAGAAGAGAACCNN4299 GGUUCUCUUCUUCUAAAUCNN 4300 NM_005080_387-405 GCUAGAAAAUCAGCUUUUANN4301 UAAAAGCUGAUUUUCUAGCNN 4302 NM_005080_628-646 UUGACUCUUCAGAUUCAGANN4303 UCUGAAUCUGAAGAGUCAANN 4304 NM_005080_656-674 CCUGUUGGGCAUUCUGGACNN4305 GUCCAGAAUGCCCAACAGGNN 4306 NM_005080_719-737 UGCCAGCCUGGAGGAGCUCNN4307 GAGCUCCUCCAGGCUGGCANN 4308 NM_005080_720-738 GCCAGCCUGGAGGAGCUCCNN4309 GGAGCUCCUCCAGGCUGGCNN 4310 NM_005080_721-739 CCAGCCUGGAGGAGCUCCCNN4311 GGGAGCUCCUCCAGGCUGGNN 4312 NM_005080_782-800 UUCUCUGUCAGUGGGGACGNN4313 CGUCCCCACUGACAGAGAANN 4314 NM_005080_867-885 GUCUUAGAGAUACCCUCUGNN4315 CAGAGGGUAUCUCUAAGACNN 4316 NM_005080_48-66 UAUGGUGGUGGUGGCAGCCNN4317 GGCUGCCACCACCACCAUANN 4318 NM_005080_963-981 UUCAUUGUCUCAGUGAAGGNN4319 CCUUCACUGAGACAAUGAANN 4320 Gene XBP-1 reference transcriptNM_005080 (human XBP-1 mRNA, FIG. 2) Notes 19mers found in both humanand rhesus

TABLE 10 XBP-1 Human/Rhesus siRNA analysis off target Oligo Name/ humanLocation of Target Anti- Anti- rhesus sequence from sense sense SenseSense Antisense Antisense Sense Sense 5′ to 3′ Count Score Count ScoreCount Score Count Score NM_005080_390-408 1 4 6 3 2 3.4 2 2NM_005080_1184-1202 2 4 3 2 1 3.2 1 2 NM_005080_1494-1512 1 4 3 3.2 12 32 3 NM_005080_1463-1481 6 3.2 5 2 4 3.2 1 2 NM_005080_610-628 3 3.2 6 36 3.2 2 2 NM_005080_823-841 4 3.2 1 2 1 3.2 4 2 NM_005080_1507-1525 33.2 2 2 3 3 2 2 NM_005080_827-845 3 3.2 1 2.2 1 3 1 2NM_005080_1503-1521 5 3.2 2 2.8 1 2 1 1 NM_005080_829-847 12 3.2 1 3 1 22 3 NM_005080_1783-1801 12 3.2 3 2.2 2 1 1 2.2 NM_005080_1183-1201 2 3 42 1 3.2 1 2 NM_005080_1501-1519 4 3 2 2.8 2 3.2 1 2.2NM_005080_1504-1522 2 3 1 2 8 3.2 1 1 NM_005080_734-752 6 3 1 2 1 3.2 32 NM_005080_893-911 9 3 1 3 13 3.2 5 3 NM_005080_1064-1082 6 3 5 3 1 3 32.2 NM_005080_1066-1084 1 3 1 2 2 3 1 2.2 NM_005080_1136-1154 7 3 1 0 53 1 2 NM_005080_1137-1155 5 3 1 2 9 3 1 0 NM_005080_1182-1200 1 3 1 2.81 3 2 2 NM_005080_1186-1204 3 3 2 2 2 3 1 1.2 NM_005080_1189-1207 1 3 32 5 3 3 2 NM_005080_1224-1242 6 3 11 2 3 3 21 2 NM_005080_1229-1247 4 36 2 1 3 3 2 NM_005080_1235-1253 7 3 3 3 5 3 2 2.2 NM_005080_1236-1254 83 2 3 7 3 1 3 NM_005080_1438-1456 10 3 2 2.2 9 3 2 2.2NM_005080_1441-1459 3 3 3 2 11 3 4 2 NM_005080_1442-1460 6 3 9 3.2 9 3 12 NM_005080_1493-1511 1 3 2 3 1 3 1 2 NM_005080_1502-1520 3 3 2 2 1 3 12 NM_005080_1506-1524 4 3 6 2 6 3 6 2 NM_005080_1594-1612 2 3 6 2 2 3 32 NM_005080_1790-1808 12 3 1 2 9 3 4 3 NM_005080_304-322 3 3 9 3 1 3 163 NM_005080_305-323 1 3 1 2 3 3 3 2.2 NM_005080_395-413 3 3 9 2 3 3 2 2NM_005080_609-627 3 3 3 3 7 3 1 2 NM_005080_611-629 2 3 2 2 1 3 2 2NM_005080_617-635 3 3 1 3 4 3 1 2.2 NM_005080_621-639 1 3 1 2.2 1 3 12.2 NM_005080_641-659 1 3 3 2 2 3 4 2 NM_005080_648-666 5 3 2 2 4 3 1 2NM_005080_651-669 4 3 1 2 5 3 10 3 NM_005080_735-753 1 3 1 2 4 3 2 2NM_005080_753-771 3 3 2 2 10 3 4 2 NM_005080_794-812 3 3 2 2 6 3 1 2NM_005080_826-844 1 3 1 2.2 4 3 13 3 NM_005080_836-854 2 3 1 3 8 3 2 3NM_005080_840-858 2 3 1 2.2 3 3 7 3 NM_005080_841-859 8 3 1 1 6 3 1 2NM_005080_847-865 10 3 1 2 5 3 1 2 NM_005080_894-912 2 3 4 3 1 3 1 3NM_005080_895-913 2 3 1 3 8 3 2 2.2 NM_005080_896-914 3 3 2 2 7 3 2 2NM_005080_899-917 3 3 1 2 7 3 6 2 NM_005080_908-926 2 3 2 2 1 3 2 3.2NM_005080_917-935 4 3 6 3.2 8 3 1 3.2 NM_005080_937-955 2 3 2 2 9 3 1 2NM_005080_950-968 7 3 1 2 12 3 1 2.8 NM_005080_1185-1203 1 3 1 2 1 2.8 12 NM_005080_1187-1205 2 3 1 2.2 2 2.8 2 2.2 NM_005080_1153-1171 6 3 2 21 2.4 3 2 NM_005080_1787-1805 1 3 1 2 1 2.4 1 2 NM_005080_606-624 4 3 22.2 1 2.4 1 1 NM_005080_1019-1037 12 3 1 1 1 2.2 2 1 NM_005080_1072-109014 3 8 2 2 2.2 9 2 NM_005080_1228-1246 1 3 6 2 1 2.2 4 2NM_005080_1461-1479 12 3 2 1 1 2.2 1 2.2 NM_005080_1495-1513 2 3 4 3 12.2 1 3 NM_005080_1496-1514 2 3 2 2.8 1 2.2 1 2.8 NM_005080_1500-1518 13 1 1.2 1 2.2 1 2.2 NM_005080_1644-1662 9 3 7 2 1 2.2 3 2NM_005080_1708-1726 3 3 1 1 1 2.2 1 2 NM_005080_302-320 1 3 5 3 1 2.2 12 NM_005080_607-625 2 3 1 2 1 2.2 3 2.2 NM_005080_824-842 4 3 1 2 1 2.24 2 NM_005080_953-971 8 3 4 2 2 2.2 5 2 NM_005080_1011-1029 2 3 4 2 1 21 2.4 NM_005080_1230-1248 2 3 1 2 3 2 2 2.2 NM_005080_1231-1249 4 3 1 21 2 4 3 NM_005080_1290-1308 7 3 1 2 1 2 1 2 NM_005080_1331-1349 4 3 5 22 2 11 2 NM_005080_1460-1478 16 3 15 3 2 2 1 2.8 NM_005080_1670-1688 1 324 3 2 2 1 2 NM_005080_1671-1689 2 3 1 2.2 1 2 2 2.2 NM_005080_1735-175321 3 3 2 2 2 4 2 NM_005080_1744-1762 1 3 1 2 1 2 2 2 NM_005080_1796-181412 3 2 0 1 2 1 0 NM_005080_343-361 7 3 7 2 1 2 1 2 NM_005080_374-392 1 33 2 1 2 2 2 NM_005080_375-393 6 3 1 1 3 2 7 1 NM_005080_608-626 1 3 1 22 2 1 2.4 NM_005080_652-670 7 3 1 2 1 2 1 2 NM_005080_686-704 9 3 1 2 92 1 2 NM_005080_909-927 3 3 2 2 2 2 1 2 NM_005080_951-969 3 3 1 2.8 6 24 2 NM_005080_952-970 8 3 3 2 1 2 5 2 NM_005080_825-843 3 3 2 2.2 1 1.26 2.2 NM_005080_1194-1212 4 3 1 2.2 2 1 2 3 NM_005080_831-849 3 3 1 2 11 3 3.2 NM_005080_835-853 1 3 1 3 1 1 2 3 NM_005080_869-887 2 3 1 2.2 11 3 3.2 NM_005080_1246-1264 3 2.8 1 2.2 1 2.8 2 2.2 NM_005080_1453-14712 2.8 8 2 3 2.8 4 2 NM_005080_1512-1530 5 2.8 10 2.2 2 2.8 11 3NM_005080_1546-1564 1 2.8 1 2 1 2.8 3 2 NM_005080_1789-1807 1 2.8 1 3 12.8 1 3 NM_005080_325-343 1 2.8 3 3 1 2.8 1 3 NM_005080_393-411 2 2.8 43 1 2.8 8 3 NM_005080_788-806 1 2.8 2 2 1 2.8 4 2 NM_005080_821-839 12.8 11 3 1 2.8 1 2 NM_005080_1514-1532 6 2.8 1 1 1 2.2 9 3NM_005080_1797-1815 1 2.8 2 1 11 2.2 1 1 NM_005080_833-851 1 2.8 3 4 22.2 4 4 NM_005080_1509-1527 1 2.8 1 2 2 2 1 2 NM_005080_1802-1820 1 2.81 1.2 1 1.2 1 1.2 NM_005080_391-409 1 2.4 1 2 1 3 1 2 NM_005080_843-8611 2.4 1 1 4 2.4 6 3 NM_005080_1508-1526 1 2.4 7 3 1 2 1 2NM_005080_1754-1772 1 2.4 4 2 1 2 1 2 NM_005080_430-448 4 2.4 1 2 1 2 32 NM_005080_437-455 1 2.4 5 2.2 1 2 4 2.2 NM_005080_1465-1483 1 2.2 22.2 2 3.2 7 3 NM_005080_1742-1760 1 2.2 2 2 13 3.2 5 3 NM_005080_438-4561 2.2 1 1 12 3.2 1 2.2 NM_005080_1060-1078 1 2.2 2 2 12 3 5 2NM_005080_1067-1085 1 2.2 2 2 6 3 1 3 NM_005080_1197-1215 2 2.2 1 3 2 31 3 NM_005080_1198-1216 1 2.2 3 3 9 3 2 3 NM_005080_1424-1442 1 2.2 12.4 7 3 1 2.4 NM_005080_1464-1482 2 2.2 4 2 1 3 6 2 NM_005080_616-634 12.2 1 3 4 3 2 3 NM_005080_757-775 1 2.2 1 2 12 3 1 2.2 NM_005080_785-8032 2.2 1 1.2 3 3 1 1 NM_005080_819-837 1 2.2 2 1 4 3 12 2NM_005080_842-860 1 2.2 1 1 2 3 6 3 NM_005080_845-863 1 2.2 4 3 1 3 11 3NM_005080_1013-1031 1 2.2 1 1 1 2.8 2 1 NM_005080_1431-1449 6 2.2 1 1.21 2.8 1 1.2 NM_005080_1673-1691 3 2.2 3 2.2 1 2.8 5 2.2NM_005080_283-301 2 2.2 2 2 5 2.8 1 2.2 NM_005080_838-856 1 2.2 1 2 12.8 1 2 NM_005080_279-297 2 2.2 7 2 1 2.4 2 1 NM_005080_633-651 1 2.2 20 1 2.4 9 2 NM_005080_1024-1042 2 2.2 9 2 1 2.2 4 2 NM_005080_1147-11652 2.2 4 1 1 2.2 1 1 NM_005080_1154-1172 1 2.2 4 2 4 2.2 5 2NM_005080_1188-1206 2 2.2 1 1 4 2.2 3 1 NM_005080_1192-1210 2 2.2 4 2 12.2 2 2 NM_005080_1195-1213 2 2.2 1 2.2 3 2.2 2 3 NM_005080_1238-1256 22.2 2 3 2 2.2 1 3 NM_005080_1548-1566 1 2.2 1 2.2 1 2.2 2 2.2NM_005080_1549-1567 3 2.2 1 2 9 2.2 3 2 NM_005080_1677-1695 1 2.2 1 2.82 2.2 2 2 NM_005080_1707-1725 1 2.2 4 2 1 2.2 2 2 NM_005080_1713-1731 12.2 1 1 3 2.2 2 2 NM_005080_1786-1804 6 2.2 1 2 6 2.2 3 2NM_005080_210-228 1 2.2 10 2 5 2.2 12 2 NM_005080_278-296 1 2.2 6 1 22.2 14 1 NM_005080_284-302 4 2.2 1 2 8 2.2 9 2 NM_005080_290-308 2 2.2 12 3 2.2 1 2 NM_005080_342-360 3 2.2 1 2 4 2.2 5 3 NM_005080_431-449 82.2 1 1 4 2.2 1 1 NM_005080_576-594 1 2.2 3 2 7 2.2 1 2NM_005080_602-620 3 2.2 2 2 2 2.2 4 2 NM_005080_618-636 2 2.2 1 3 1 2.21 3 NM_005080_678-696 1 2.2 1 1 6 2.2 1 2 NM_005080_796-814 4 2.2 1 3 12.2 2 2.2 NM_005080_940-958 1 2.2 9 3 3 2.2 1 2 NM_005080_954-972 5 2.29 2 3 2.2 1 1 NM_005080_977-995 2 2.2 1 2 1 2.2 1 1.2NM_005080_1018-1036 1 2.2 1 1 2 2 1 1 NM_005080_1026-1044 2 2.2 8 2 1 22 2 NM_005080_1138-1156 1 2.2 1 2 1 2 1 0 NM_005080_1141-1159 1 2.2 3 21 2 8 2 NM_005080_1142-1160 2 2.2 2 2.2 2 2 1 2.8 NM_005080_1155-1173 12.2 3 2 2 2 3 2 NM_005080_1158-1176 1 2.2 1 2.2 1 2 1 2NM_005080_1193-1211 2 2.2 1 2 2 2 1 2 NM_005080_1196-1214 2 2.2 2 3 5 22 2.8 NM_005080_1219-1237 2 2.2 3 2 3 2 7 2.2 NM_005080_107-125 3 2.2 10 1 2 2 0 NM_005080_108-126 4 2.2 1 0 1 2 2 0 NM_005080_1505-1523 1 2.21 2 5 2 1 2 NM_005080_1567-1585 4 2.2 1 1.2 1 2 1 2 NM_005080_1672-16902 2.2 2 2.2 1 2 6 3 NM_005080_1678-1696 4 2.2 1 2.8 1 2 2 2.8NM_005080_1778-1796 4 2.2 7 2 2 2 9 2 NM_005080_1779-1797 1 2.2 9 2 4 21 1 NM_005080_280-298 5 2.2 7 2 1 2 2 1 NM_005080_282-300 2 2.2 2 2 1 22 2 NM_005080_288-306 1 2.2 1 1 2 2 1 1 NM_005080_291-309 3 2.2 2 2 5 21 2 NM_005080_347-365 3 2.2 2 2.4 1 2 4 3 NM_005080_397-415 4 2.2 20 3 12 1 2.2 NM_005080_398-416 1 2.2 1 2.2 2 2 1 2.2 NM_005080_399-417 2 2.21 2 2 2 3 2.2 NM_005080_512-530 2 2.2 1 2 1 2 9 2 NM_005080_517-535 22.2 1 0 1 2 1 0 NM_005080_596-614 1 2.2 5 2 3 2 4 2 NM_005080_598-616 12.2 4 2 3 2 7 2 NM_005080_601-619 2 2.2 8 3 1 2 1 2.2 NM_005080_605-6232 2.2 5 2 5 2 9 2 NM_005080_661-679 2 2.2 8 2 1 2 1 1 NM_005080_688-7061 2.2 2 0 2 2 2 1 NM_005080_691-709 2 2.2 8 2 2 2 15 2 NM_005080_828-8461 2.2 3 3.2 1 2 1 2 NM_005080_830-848 8 2.2 1 2.8 2 2 2 3NM_005080_834-852 2 2.2 6 3 3 2 3 3 NM_005080_846-864 2 2.2 1 2 1 2 1 2NM_005080_870-888 4 2.2 1 2.2 1 2 7 3.2 NM_005080_891-909 2 2.2 6 2 2 25 2 NM_005080_900-918 2 2.2 1 2 2 2 1 2.2 NM_005080_911-929 3 2.2 2 3 12 1 2.2 NM_005080_912-930 3 2.2 7 3.2 1 2 1 2.2 NM_005080_979-997 5 2.22 2 1 2 5 2.2 NM_005080_1366-1384 5 2.2 2 1.2 1 1.2 1 1.2NM_005080_150-168 4 2.2 8 1 1 1.2 1 2 NM_005080_1437-1455 1 2.2 2 2.2 11 1 2 NM_005080_482-500 5 2.2 4 2 6 1 4 2 NM_005080_580-598 1 2.2 1 2 11 3 2 NM_005080_613-631 1 2 6 3 2 4.2 2 3 NM_005080_1065-1083 4 2 1 3.43 4 3 2.2 NM_005080_614-632 1 2 1 2 8 3.2 1 2 NM_005080_640-658 1 2 3 23 3.2 1 2 NM_005080_1014-1032 2 2 1 2 16 3 2 2 NM_005080_1015-1033 3 2 21.2 1 3 1 2.2 NM_005080_1146-1164 1 2 3 2 28 3 2 2 NM_005080_1232-1250 12 1 2 5 3 1 3 NM_005080_1234-1252 1 2 1 2 1 3 1 2.2 NM_005080_1237-12551 2 4 3 10 3 5 3 NM_005080_1443-1461 1 2 2 2 9 3 6 2.2NM_005080_1462-1480 2 2 2 2 4 3 3 3 NM_005080_1510-1528 1 2 1 2 4 3 1 2NM_005080_1591-1609 3 2 1 1 4 3 2 1.2 NM_005080_1615-1633 1 2 1 2 2 3 82 NM_005080_1716-1734 4 2 6 3 9 3 1 1 NM_005080_1718-1736 1 2 7 3 20 3 12.2 NM_005080_1725-1743 1 2 1 2.2 16 3 2 2 NM_005080_1748-1766 1 2 1 4 73 2 3.2 NM_005080_1780-1798 2 2 4 2 5 3 9 2 NM_005080_1794-1812 2 2 1 26 3 2 2 NM_005080_156-174 2 2 4 2 21 3 2 1 NM_005080_299-317 1 2 2 2 103 2 2 NM_005080_344-362 1 2 5 2.2 7 3 1 2.2 NM_005080_371-389 3 2 6 3 203 1 2.2 NM_005080_373-391 1 2 3 2 5 3 1 2 NM_005080_524-542 4 2 2 2 3 34 3 NM_005080_525-543 3 2 6 2 6 3 3 2 NM_005080_612-630 1 2 3 2 1 3 8 3NM_005080_615-633 1 2 1 2 1 3 1 2 NM_005080_645-663 1 2 1 1 6 3 3 1NM_005080_792-810 1 2 2 2.2 10 3 2 2 NM_005080_905-923 2 2 1 2.2 1 3 4 3NM_005080_976-994 1 2 4 2 4 3 4 2 NM_005080_1244-1262 3 2 7 2 1 2.8 5 2NM_005080_1791-1809 5 2 4 2 1 2.8 2 2.8 NM_005080_755-773 5 2 4 2 1 2.84 2 NM_005080_799-817 3 2 2 2 1 2.8 16 2 NM_005080_832-850 3 2 3 3 1 2.84 3 NM_005080_839-857 1 2 2 2.2 1 2.8 3 2 NM_005080_100-118 3 2 6 2 12.4 2 1 NM_005080_281-299 7 2 3 2 1 2.4 10 2 NM_005080_822-840 1 2 5 2.21 2.4 1 2.2 NM_005080_1152-1170 1 2 3 2 3 2.2 2 2.2 NM_005080_1191-12093 2 4 1 1 2.2 3 2 NM_005080_1225-1243 2 2 5 2 2 2.2 1 1NM_005080_1227-1245 3 2 1 1 1 2.2 1 1 NM_005080_1239-1257 2 2 1 2 5 2.21 2 NM_005080_1430-1448 2 2 2 2 4 2.2 2 2.2 NM_005080_1499-1517 1 2 42.2 4 2.2 10 2.2 NM_005080_1553-1571 1 2 2 2.2 2 2.2 8 2NM_005080_1585-1603 1 2 1 2 5 2.2 1 1 NM_005080_1592-1610 3 2 2 2 2 2.23 2 NM_005080_1743-1761 1 2 2 2 1 2.2 4 2 NM_005080_154-172 1 2 1 2.2 22.2 5 3 NM_005080_193-211 1 2 1 1 10 2.2 1 1 NM_005080_199-217 10 2 3 25 2.2 4 3 NM_005080_292-310 5 2 3 2 1 2.2 2 2 NM_005080_341-359 1 2 1 22 2.2 1 2.2 NM_005080_377-395 4 2 1 1 5 2.2 7 2 NM_005080_519-537 1 2 31 12 2.2 4 2 NM_005080_522-540 2 2 8 2 1 2.2 5 2 NM_005080_577-595 2 2 62 8 2.2 3 2 NM_005080_599-617 4 2 5 2 7 2.2 5 2 NM_005080_754-772 2 2 53 1 2.2 1 2 NM_005080_888-906 1 2 1 2.2 4 2.2 1 2 NM_005080_939-957 1 21 2.8 2 2.2 1 2 NM_005080_964-982 1 2 1 1 1 2.2 4 2 NM_005080_1012-10306 2 4 3 4 2 3 3.2 NM_005080_1016-1034 4 2 2 1.2 1 2 10 3NM_005080_1020-1038 7 2 2 2 2 2 4 2 NM_005080_1025-1043 2 2 9 2 3 2 22.2 NM_005080_1027-1045 1 2 1 2 1 2 1 2 NM_005080_1028-1046 1 2 5 2 3 28 2 NM_005080_1030-1048 1 2 2 2 1 2 1 2 NM_005080_1031-1049 16 2 2 2 4 21 2 NM_005080_1032-1050 3 2 21 3 2 2 4 2.8 NM_005080_1033-1051 11 2 1 27 2 2 2.2 NM_005080_1056-1074 1 2 6 2 2 2 13 2 NM_005080_1057-1075 3 2 22.2 2 2 1 2 NM_005080_1058-1076 4 2 2 1 5 2 2 1 NM_005080_1059-1077 5 22 2 13 2 3 2 NM_005080_1061-1079 4 2 3 2 16 2 1 1.2 NM_005080_1063-108111 2 3 2 1 2 4 2 NM_005080_1069-1087 2 2 10 3 1 2 1 2NM_005080_1071-1089 2 2 2 3 1 2 2 3 NM_005080_1073-1091 4 2 12 3 4 2 3 2NM_005080_1075-1093 6 2 2 2.2 6 2 3 2.2 NM_005080_1076-1094 7 2 4 3 7 21 3 NM_005080_1078-1096 4 2 3 2 3 2 12 2 NM_005080_1139-1157 1 2 2 2 2 21 0 NM_005080_1140-1158 4 2 3 2 2 2 1 2 NM_005080_1143-1161 2 2 2 2.2 32 1 3 NM_005080_1144-1162 1 2 2 2 1 2 3 2 NM_005080_1145-1163 1 2 1 2.21 2 2 2 NM_005080_1148-1166 2 2 4 2 1 2 2 2 NM_005080_1156-1174 12 2 12.2 6 2 1 2 NM_005080_1157-1175 1 2 2 2 1 2 1 1 NM_005080_1159-1177 1 21 2 4 2 3 2 NM_005080_1160-1178 1 2 1 1.2 3 2 2 2 NM_005080_1190-1208 12 2 2.2 5 2 2 2 NM_005080_1218-1236 2 2 1 2 16 2 4 2.2NM_005080_1220-1238 5 2 1 1 4 2 1 1 NM_005080_1221-1239 5 2 1 1 10 2 1 1NM_005080_1233-1251 1 2 3 3 1 2 1 3 NM_005080_1240-1258 6 2 1 2 4 2 1 2NM_005080_1241-1259 13 2 2 2 13 2 1 2 NM_005080_1242-1260 3 2 3 2 4 2 32 NM_005080_1243-1261 1 2 2 2 2 2 1 2.8 NM_005080_1282-1300 12 2 5 2 8 22 1 NM_005080_1287-1305 6 2 3 2 10 2 1 2 NM_005080_1289-1307 2 2 21 3 12 4 2.2 NM_005080_1310-1328 1 2 3 2 3 2 1 2.2 NM_005080_1330-1348 6 2 22 4 2 7 2 NM_005080_1332-1350 2 2 8 3 1 2 12 3 NM_005080_1333-1351 2 2 12 1 2 1 2 NM_005080_1369-1387 4 2 3 2 4 2 4 2 NM_005080_1370-1388 1 2 72 1 2 5 2 NM_005080_1371-1389 4 2 2 2 8 2 1 1 NM_005080_101-119 1 2 2 22 2 2 1 NM_005080_1418-1436 2 2 1 1 3 2 11 2 NM_005080_1419-1437 3 2 3 29 2 8 2.2 NM_005080_1422-1440 6 2 11 3 1 2 6 3 NM_005080_102-120 3 2 1 25 2 8 2 NM_005080_1423-1441 6 2 4 3 4 2 6 3 NM_005080_1425-1443 1 2 2 21 2 1 2 NM_005080_1427-1445 5 2 1 2 11 2 1 2 NM_005080_1428-1446 6 2 12.2 7 2 1 2 NM_005080_1429-1447 1 2 5 3 1 2 3 3 NM_005080_1432-1450 3 23 2 2 2 1 2.8 NM_005080_1433-1451 3 2 4 2 4 2 6 2 NM_005080_1435-1453 12 1 2 2 2 4 2 NM_005080_1439-1457 1 2 1 2 2 2 4 2 NM_005080_104-122 1 25 3 4 2 7 2 NM_005080_1444-1462 3 2 4 2 1 2 2 2 NM_005080_1445-1463 10 23 2 17 2 3 2 NM_005080_1446-1464 8 2 2 2 18 2 1 1 NM_005080_1447-1465 12 2 2.2 3 2 3 2 NM_005080_1448-1466 2 2 1 2 2 2 5 2 NM_005080_1451-14692 2 1 1 1 2 1 1 NM_005080_1454-1472 2 2 4 2 4 2 4 2 NM_005080_1458-14766 2 3 2 4 2 10 2 NM_005080_1459-1477 1 2 3 2 3 2 1 1.2 NM_005080_106-1242 2 1 1.2 1 2 9 2.2 NM_005080_1466-1484 1 2 2 2 2 2 2 2NM_005080_1486-1504 2 2 3 2 2 2 1 0 NM_005080_1487-1505 2 2 3 2 2 2 1 1NM_005080_1489-1507 4 2 5 2 1 2 1 1 NM_005080_1490-1508 3 2 2 2 6 2 4 2NM_005080_1491-1509 3 2 2 2 2 2 2 2.2 NM_005080_109-127 5 2 1 1 4 2 2 1NM_005080_1497-1515 1 2 2 3.2 1 2 2 3 NM_005080_1498-1516 2 2 2 2.2 4 21 2 NM_005080_110-128 3 2 2 1 4 2 1 1 NM_005080_1511-1529 2 2 10 2 3 2 82 NM_005080_1513-1531 5 2 1 1 3 2 1 2.8 NM_005080_1516-1534 1 2 1 2 1 22 2.2 NM_005080_1517-1535 2 2 1 1 2 2 2 1 NM_005080_1518-1536 4 2 2 2 22 3 2 NM_005080_1547-1565 2 2 1 2 4 2 2 2 NM_005080_1550-1568 5 2 2 2 42 5 2 NM_005080_1551-1569 1 2 2 1.2 1 2 1 1.2 NM_005080_1552-1570 4 2 11.2 4 2 1 1.2 NM_005080_1554-1572 3 2 1 1 7 2 1 1.2 NM_005080_1559-15775 2 1 2 7 2 1 2 NM_005080_1560-1578 5 2 1 1 5 2 1 1 NM_005080_1563-15815 2 1 1.2 18 2 1 1 NM_005080_1565-1583 7 2 2 1.2 11 2 3 1.2NM_005080_1566-1584 6 2 1 1.2 9 2 9 1.2 NM_005080_1570-1588 2 2 1 2 5 21 2.2 NM_005080_1573-1591 2 2 9 2 1 2 5 2 NM_005080_1578-1596 2 2 1 2 52 3 2 NM_005080_1579-1597 3 2 4 2 4 2 3 2 NM_005080_1580-1598 3 2 2 2 42 5 2 NM_005080_1581-1599 3 2 5 2 2 2 5 2 NM_005080_1583-1601 4 2 4 2 42 1 1 NM_005080_1584-1602 7 2 7 2 9 2 1 0 NM_005080_1586-1604 4 2 1 1 32 2 1 NM_005080_1589-1607 1 2 3 2 1 2 1 2 NM_005080_1590-1608 4 2 9 3 42 1 2 NM_005080_1595-1613 1 2 10 2 1 2 6 2 NM_005080_1616-1634 3 2 1 2 12 2 2 NM_005080_1617-1635 2 2 1 1 1 2 3 1 NM_005080_1643-1661 2 2 5 2 32 1 1.2 NM_005080_1645-1663 1 2 2 1 1 2 1 1 NM_005080_1646-1664 3 2 5 13 2 1 1 NM_005080_1647-1665 4 2 7 2 1 2 4 2 NM_005080_1648-1666 7 2 4 25 2 10 2 NM_005080_1649-1667 2 2 9 2 5 2 14 2 NM_005080_1679-1697 5 2 22.2 5 2 2 2.2 NM_005080_1680-1698 2 2 1 2.2 3 2 1 2.2NM_005080_1681-1699 7 2 1 2 7 2 1 3 NM_005080_1682-1700 12 2 1 2 19 2 12.2 NM_005080_1683-1701 6 2 15 3 7 2 3 3 NM_005080_1684-1702 5 2 3 3 6 21 3 NM_005080_1687-1705 4 2 4 1 2 2 1 1 NM_005080_1709-1727 1 2 6 2 1 25 2 NM_005080_1710-1728 3 2 6 2 2 2 5 2 NM_005080_1711-1729 1 2 1 1 2 21 1.2 NM_005080_1712-1730 10 2 1 2 10 2 1 2.2 NM_005080_1714-1732 1 2 12 1 2 2 1 NM_005080_1715-1733 2 2 1 2 3 2 1 1 NM_005080_1717-1735 4 2 43 2 2 1 2.2 NM_005080_1719-1737 7 2 1 2 13 2 2 2 NM_005080_1721-1739 1 28 3 1 2 5 3 NM_005080_1722-1740 4 2 10 3 2 2 6 3 NM_005080_1723-1741 1 21 2 3 2 4 2.2 NM_005080_1726-1744 2 2 1 2.8 11 2 1 2.2NM_005080_1727-1745 3 2 1 2 10 2 17 3 NM_005080_1728-1746 10 2 2 2 3 2 12 NM_005080_1729-1747 7 2 1 1 4 2 3 1 NM_005080_1736-1754 10 2 1 2 2 2 42 NM_005080_1739-1757 1 2 8 2 1 2 8 2 NM_005080_1746-1764 2 2 4 2.2 1 21 2 NM_005080_1747-1765 3 2 3 3 1 2 1 2.2 NM_005080_1749-1767 3 2 1 2.23 2 2 3 NM_005080_1750-1768 6 2 1 2 13 2 2 2 NM_005080_1751-1769 5 2 3 214 2 2 2 NM_005080_1752-1770 3 2 6 2 1 2 1 2 NM_005080_1753-1771 1 2 7 23 2 1 2 NM_005080_1755-1773 7 2 2 2 1 2 1 2 NM_005080_1758-1776 7 2 7 212 2 3 2 NM_005080_1781-1799 1 2 1 1.2 1 2 7 2 NM_005080_1782-1800 1 2 12 3 2 2 2 NM_005080_1784-1802 2 2 3 3 1 2 1 2 NM_005080_1785-1803 4 2 12.2 2 2 1 2.2 NM_005080_1788-1806 1 2 3 3 7 2 3 2.2 NM_005080_1792-18102 2 1 2.8 1 2 2 2.8 NM_005080_1793-1811 3 2 2 2 1 2 1 2.8NM_005080_1795-1813 5 2 1 2.4 1 2 2 2 NM_005080_1798-1816 1 2 7 2 1 2 52 NM_005080_1799-1817 1 2 4 2 1 2 5 2 NM_005080_1800-1818 5 2 3 2 4 2 12 NM_005080_1801-1819 2 2 3 2.2 4 2 2 1 NM_005080_146-164 4 2 2 1 1 2 11 NM_005080_147-165 2 2 2 1 1 2 23 2 NM_005080_148-166 1 2 3 2 1 2 4 2NM_005080_149-167 1 2 1 1.2 2 2 1 1.2 NM_005080_155-173 5 2 3 2 2 2 3 1NM_005080_157-175 7 2 7 2 5 2 11 2 NM_005080_158-176 4 2 7 2 6 2 1 1NM_005080_159-177 4 2 5 2.2 3 2 1 1.2 NM_005080_188-206 4 2 1 1 8 2 2 1NM_005080_189-207 1 2 1 1 2 2 3 1 NM_005080_195-213 4 2 2 1 5 2 6 2NM_005080_196-214 4 2 2 1 2 2 2 2.2 NM_005080_197-215 2 2 3 2 1 2 1 2.2NM_005080_198-216 4 2 1 2 4 2 2 2 NM_005080_205-223 5 2 6 1 6 2 1 0NM_005080_206-224 7 2 8 1 1 2 10 1 NM_005080_207-225 5 2 3 1 4 2 3 1NM_005080_211-229 2 2 15 2 2 2 3 2 NM_005080_250-268 16 2 8 2 6 2 1 0NM_005080_256-274 11 2 1 0 7 2 2 0 NM_005080_263-281 6 2 4 2.2 4 2 2 1NM_005080_264-282 5 2 1 2.2 4 2 2 2 NM_005080_285-303 2 2 3 3 3 2 14 3NM_005080_286-304 8 2 1 2 9 2 2 2 NM_005080_287-305 8 2 1 0 5 2 1 0NM_005080_294-312 5 2 2 2 1 2 1 2 NM_005080_295-313 1 2 1 0 1 2 3 2NM_005080_296-314 1 2 2 1.2 1 2 2 2.2 NM_005080_298-316 1 2 1 2.2 4 2 32 NM_005080_303-321 1 2 1 2 1 2 1 2 NM_005080_332-350 8 2 1 2 11 2 1 2NM_005080_339-357 3 2 1 1 1 2 1 1 NM_005080_340-358 3 2 2 2 2 2 1 2NM_005080_345-363 1 2 5 2.2 6 2 1 2.2 NM_005080_346-364 2 2 5 3 1 2 1 3NM_005080_348-366 1 2 3 2 1 2 2 2 NM_005080_349-367 4 2 5 2 1 2 8 2NM_005080_352-370 3 2 3 2.2 6 2 3 2.2 NM_005080_353-371 3 2 1 2.2 2 2 12.2 NM_005080_354-372 8 2 7 2 12 2 4 2 NM_005080_355-373 6 2 1 2 3 2 1 3NM_005080_361-379 2 2 2 1 5 2 1 1 NM_005080_366-384 2 2 2 2 4 2 12 2.2NM_005080_369-387 9 2 3 2.2 4 2 6 2 NM_005080_370-388 9 2 2 2 13 2 6 2NM_005080_372-390 3 2 1 2 1 2 1 2.2 NM_005080_376-394 2 2 1 1 2 2 1 1NM_005080_381-399 8 2 2 2.2 5 2 1 1 NM_005080_384-402 2 2 4 2.2 3 2 8 2NM_005080_388-406 1 2 1 1 1 2 1 1 NM_005080_392-410 1 2 1 2.2 1 2 1 2.2NM_005080_394-412 1 2 2 3 1 2 9 3 NM_005080_396-414 1 2 2 2 2 2 2 3NM_005080_400-418 6 2 3 0 18 2 1 0 NM_005080_421-439 2 2 9 2.2 1 2 9 1.2NM_005080_422-440 1 2 1 2 1 2 1 1 NM_005080_423-441 1 2 1 2 1 2 1 1NM_005080_425-443 3 2 6 3 7 2 2 2 NM_005080_428-446 4 2 1 2.2 4 2 2 2.2NM_005080_429-447 3 2 4 2.8 3 2 1 2 NM_005080_432-450 4 2 5 2 1 2 1 2NM_005080_433-451 10 2 5 2 5 2 1 2 NM_005080_434-452 5 2 3 2.2 3 2 4 1NM_005080_435-453 6 2 2 3 4 2 4 1 NM_005080_436-454 4 2 1 2 7 2 4 2.2NM_005080_459-477 2 2 2 2.2 3 2 4 2.2 NM_005080_460-478 1 2 5 3 2 2 4 2NM_005080_462-480 1 2 1 2 2 2 2 2 NM_005080_486-504 5 2 1 1 3 2 1 1NM_005080_510-528 3 2 1 1 4 2 9 2 NM_005080_513-531 2 2 2 2 1 2 1 2NM_005080_514-532 3 2 10 2 8 2 1 0 NM_005080_515-533 1 2 7 2 3 2 1 0NM_005080_516-534 4 2 1 0 7 2 1 0 NM_005080_520-538 1 2 3 1 13 2 3 2NM_005080_521-539 2 2 1 1 11 2 2 2 NM_005080_523-541 6 2 2 2 2 2 2 2NM_005080_578-596 2 2 2 2 6 2 1 2 NM_005080_581-599 4 2 1 1 2 2 1 1NM_005080_582-600 3 2 1 2 4 2 1 2 NM_005080_583-601 4 2 2 2 17 2 1 2NM_005080_584-602 5 2 2 2 17 2 1 2 NM_005080_585-603 3 2 2 2 4 2 2 2NM_005080_586-604 1 2 2 2 1 2 1 2.2 NM_005080_587-605 3 2 6 3 4 2 1 2.2NM_005080_588-606 3 2 1 2 3 2 24 3 NM_005080_589-607 2 2 1 1 3 2 1 1NM_005080_590-608 1 2 1 2 3 2 1 2 NM_005080_591-609 3 2 1 2.2 5 2 7 2.2NM_005080_597-615 2 2 1 2.2 1 2 5 2.2 NM_005080_600-618 1 2 1 2.2 3 2 92 NM_005080_603-621 4 2 3 2 4 2 3 2 NM_005080_619-637 3 2 4 3.2 1 2 73.2 NM_005080_620-638 5 2 2 4.2 1 2 1 3 NM_005080_622-640 1 2 1 2.2 2 21 2.2 NM_005080_623-641 3 2 1 3 1 2 2 3 NM_005080_624-642 2 2 1 3 1 2 12 NM_005080_625-643 8 2 4 2.8 19 2 2 2 NM_005080_626-644 9 2 1 2.8 5 2 12 NM_005080_629-647 2 2 4 1 1 2 4 1 NM_005080_632-650 1 2 2 0 3 2 7 1NM_005080_634-652 6 2 2 1 4 2 7 2 NM_005080_637-655 2 2 2 2 2 2 1 2NM_005080_638-656 2 2 5 3 8 2 3 3 NM_005080_639-657 1 2 1 2 1 2 1 2NM_005080_642-660 2 2 1 1 2 2 2 2 NM_005080_643-661 1 2 3 2 3 2 4 3NM_005080_644-662 2 2 4 3 3 2 6 2.2 NM_005080_646-664 2 2 2 1 5 2 1 1NM_005080_649-667 1 2 2 2 1 2 1 2 NM_005080_650-668 1 2 1 2 1 2 1 3NM_005080_653-671 2 2 2 2 2 2 2 2 NM_005080_658-676 2 2 2 1 1 2 1 1NM_005080_659-677 2 2 2 2 2 2 1 2 NM_005080_660-678 1 2 6 2 2 2 1 1NM_005080_663-681 6 2 5 2 2 2 2 2 NM_005080_664-682 4 2 4 2 1 2 9 2.2NM_005080_668-686 6 2 2 2.2 3 2 4 2.2 NM_005080_671-689 1 2 2 1 10 2 112 NM_005080_676-694 3 2 1 2 4 2 9 3 NM_005080_677-695 2 2 1 2 1 2 2 2NM_005080_679-697 1 2 1 2 1 2 1 2 NM_005080_680-698 2 2 5 3 1 2 19 3.2NM_005080_682-700 7 2 2 2 4 2 1 2 NM_005080_687-705 1 2 3 1 2 2 6 1NM_005080_689-707 2 2 1 2 3 2 2 2 NM_005080_695-713 2 2 1 2 1 2 1 2NM_005080_696-714 3 2 1 1 1 2 1 2 NM_005080_698-716 11 2 1 2 11 2 1 2NM_005080_731-749 1 2 1 1 1 2 1 2.2 NM_005080_732-750 1 2 2 2 1 2 1 2NM_005080_733-751 1 2 1 2.8 1 2 1 2 NM_005080_736-754 1 2 2 2 4 2 4 2NM_005080_737-755 1 2 6 3 4 2 1 2 NM_005080_738-756 2 2 2 2.2 7 2 3 2.2NM_005080_740-758 4 2 7 3 5 2 1 3 NM_005080_741-759 3 2 5 3 1 2 1 3NM_005080_742-760 1 2 4 3 3 2 1 3 NM_005080_743-761 4 2 2 2 6 2 5 3NM_005080_748-766 6 2 1 1.2 4 2 2 2 NM_005080_749-767 5 2 2 2 2 2 2 2NM_005080_750-768 4 2 3 2 2 2 2 2 NM_005080_751-769 4 2 1 2 1 2 1 2.2NM_005080_752-770 7 2 2 2 3 2 1 2 NM_005080_756-774 3 2 2 2 3 2 8 3NM_005080_758-776 1 2 1 2 1 2 1 1 NM_005080_759-777 4 2 2 2 4 2 2 2NM_005080_760-778 1 2 1 2 3 2 1 2 NM_005080_761-779 5 2 1 2.2 3 2 1 2NM_005080_762-780 7 2 2 2.2 1 2 1 2.2 NM_005080_767-785 5 2 4 2 5 2 1 1NM_005080_769-787 4 2 1 1.2 7 2 5 2 NM_005080_773-791 14 2 2 1 7 2 3 1NM_005080_779-797 6 2 6 2 21 2 9 2 NM_005080_786-804 1 2 1 1.2 1 2 1 1NM_005080_787-805 2 2 2 2 1 2 2 2 NM_005080_789-807 1 2 4 2.2 1 2 6 2.2NM_005080_793-811 4 2 1 2 11 2 1 2 NM_005080_795-813 1 2 4 3 1 2 1 3NM_005080_797-815 3 2 5 3.2 3 2 1 2 NM_005080_798-816 4 2 2 2.8 1 2 1 1NM_005080_800-818 5 2 2 1 3 2 1 1 NM_005080_804-822 9 2 2 1 8 2 2 0NM_005080_806-824 11 2 3 2 11 2 5 2 NM_005080_807-825 2 2 4 2.2 1 2 2 2NM_005080_808-826 2 2 1 2.2 1 2 1 2.2 NM_005080_809-827 3 2 7 2 4 2 10 2NM_005080_810-828 1 2 5 2 3 2 2 2 NM_005080_811-829 1 2 1 1 1 2 1 1NM_005080_813-831 6 2 2 2 7 2 2 2 NM_005080_814-832 1 2 1 2 1 2 1 2NM_005080_818-836 4 2 1 2.2 2 2 1 2.2 NM_005080_820-838 1 2 5 2 1 2 1 2NM_005080_837-855 1 2 3 2.8 6 2 1 2.2 NM_005080_844-862 4 2 3 2 13 2 12.2 NM_005080_872-890 2 2 1 3 4 2 1 3 NM_005080_873-891 1 2 4 2 3 2 1 2NM_005080_874-892 4 2 7 3.2 2 2 1 2.4 NM_005080_876-894 6 2 1 2.2 4 2 42.2 NM_005080_889-907 1 2 2 2.2 1 2 2 2 NM_005080_890-908 2 2 1 3 3 2 12 NM_005080_897-915 1 2 2 3 5 2 4 3 NM_005080_898-916 1 2 2 3 1 2 7 3NM_005080_901-919 4 2 3 2.2 3 2 2 2.2 NM_005080_903-921 1 2 2 2 4 2 1 1NM_005080_904-922 1 2 3 2.2 4 2 1 2 NM_005080_906-924 2 2 4 3 2 2 5 3NM_005080_907-925 1 2 4 3 2 2 3 3 NM_005080_910-928 5 2 2 2 4 2 1 1NM_005080_913-931 4 2 1 3.2 3 2 3 3.2 NM_005080_916-934 3 2 7 3 3 2 4 3NM_005080_918-936 1 2 2 3 1 2 3 3 NM_005080_919-937 3 2 3 3 1 2 4 3NM_005080_920-938 2 2 2 2 2 2 2 2 NM_005080_922-940 5 2 4 2 9 2 3 2.2NM_005080_923-941 3 2 3 2 14 2 1 2 NM_005080_929-947 8 2 8 2 5 2 5 2NM_005080_930-948 6 2 4 2 5 2 1 2 NM_005080_931-949 3 2 1 2.2 2 2 10 3NM_005080_932-950 1 2 3 2 4 2 2 2 NM_005080_933-951 5 2 10 3 2 2 4 2NM_005080_934-952 1 2 2 2.2 6 2 5 2 NM_005080_935-953 2 2 3 2 7 2 1 2NM_005080_936-954 4 2 8 3 2 2 7 3 NM_005080_938-956 1 2 1 2 1 2 1 2NM_005080_941-959 3 2 2 2 5 2 2 2 NM_005080_942-960 1 2 1 2 1 2 1 1.2NM_005080_943-961 2 2 1 2 2 2 1 2 NM_005080_944-962 3 2 3 3 6 2 1 2.2NM_005080_946-964 1 2 2 3 2 2 9 3 NM_005080_947-965 1 2 2 2 2 2 4 2NM_005080_948-966 3 2 1 2.2 4 2 4 2.2 NM_005080_949-967 1 2 1 2 3 2 4 2NM_005080_955-973 5 2 2 2 4 2 3 2 NM_005080_956-974 2 2 9 2 2 2 4 2NM_005080_957-975 2 2 3 2 1 2 2 2.2 NM_005080_960-978 7 2 2 1 2 2 1 1NM_005080_961-979 2 2 2 2 1 2 3 2 NM_005080_965-983 2 2 1 1 2 2 3 2NM_005080_967-985 8 2 1 2 3 2 1 2 NM_005080_968-986 12 2 1 2.2 13 2 22.2 NM_005080_971-989 3 2 12 3 7 2 1 2 NM_005080_972-990 8 2 3 2 23 2 22 NM_005080_973-991 6 2 1 1 8 2 1 2 NM_005080_980-998 8 2 3 2.2 7 2 1 2NM_005080_984-1002 14 2 3 2 18 2 1 2 NM_005080_986-1004 1 2 2 2 5 2 2 2NM_005080_1023-1041 1 2 1 1.2 1 1.2 1 1.2 NM_005080_1151-1169 2 2 3 2 61.2 5 2 NM_005080_1367-1385 9 2 1 2.2 1 1.2 4 2.8 NM_005080_1414-1432 22 1 1 1 1.2 7 2 NM_005080_1415-1433 7 2 1 1 1 1.2 4 1NM_005080_1674-1692 3 2 8 3 1 1.2 3 2 NM_005080_1675-1693 1 2 2 2 1 1.26 2 NM_005080_330-348 4 2 6 2 1 1.2 2 2 NM_005080_333-351 8 2 2 1 2 1.24 2 NM_005080_592-610 3 2 3 2 1 1.2 1 2.2 NM_005080_665-683 3 2 2 2 31.2 1 2.8 NM_005080_815-833 3 2 2 2 2 1.2 1 2 NM_005080_1029-1047 1 2 32.2 2 1 9 3 NM_005080_1077-1095 9 2 1 3 1 1 1 3.2 NM_005080_1222-1240 32 2 1 1 1 4 1 NM_005080_1285-1303 13 2 1 2 1 1 1 2 NM_005080_1334-1352 22 1 3 1 1 1 2 NM_005080_1335-1353 4 2 1 2.2 1 1 6 3 NM_005080_1436-14543 2 4 2 1 1 2 2 NM_005080_1449-1467 3 2 3 3 1 1 9 3 NM_005080_1450-14681 2 1 2.2 1 1 4 2.2 NM_005080_114-132 13 2 1 0 1 1 7 2NM_005080_1555-1573 2 2 2 1 1 1 1 1 NM_005080_1556-1574 5 2 1 1 1 1 2 2NM_005080_1561-1579 5 2 2 1 1 1 7 1 NM_005080_1562-1580 7 2 1 1 1 1 1 1NM_005080_1569-1587 1 2 2 2 5 1 4 2.2 NM_005080_1588-1606 2 2 2 1 1 1 11 NM_005080_1640-1658 1 2 2 2 1 1 3 2 NM_005080_1641-1659 2 2 1 2 1 1 12 NM_005080_1642-1660 5 2 2 2 2 1 1 2 NM_005080_1650-1668 1 2 4 2 1 1 42 NM_005080_1686-1704 6 2 1 2.2 1 1 2 2.2 NM_005080_1745-1763 1 2 1 2 11 1 2 NM_005080_138-156 21 2 2 1 1 1 1 1 NM_005080_145-163 10 2 5 1 1 13 1 NM_005080_190-208 4 2 3 2 1 1 2 1 NM_005080_191-209 13 2 3 1 2 1 5 1NM_005080_192-210 5 2 1 1 1 1 1 1 NM_005080_259-277 6 2 1 1 3 1 3 1NM_005080_261-279 19 2 1 1 2 1 1 0 NM_005080_289-307 1 2 1 1 2 1 1 1NM_005080_363-381 15 2 5 2 2 1 6 2 NM_005080_365-383 5 2 2 2 2 1 3 1.2NM_005080_385-403 4 2 3 2 1 1 9 2 NM_005080_461-479 1 2 1 1.2 2 1 5 2.2NM_005080_490-508 3 2 1 3 1 1 3 3 NM_005080_518-536 3 2 1 1 2 1 1 1NM_005080_673-691 6 2 3 2.2 2 1 2 2.2 NM_005080_685-703 1 2 3 2 1 1 3 2NM_005080_730-748 3 2 4 2 1 1 1 2 NM_005080_772-790 3 2 1 2 1 1 7 2NM_005080_801-819 5 2 1 1 1 1 2 1 NM_005080_817-835 2 2 1 2 1 1 3 2NM_005080_887-905 3 2 1 2.2 1 1 2 2 NM_005080_924-942 7 2 2 1 4 1 1 1NM_005080_927-945 13 2 3 2 4 1 6 2 NM_005080_928-946 1 2 3 2 1 1 2 2.8NM_005080_974-992 4 2 1 1 2 1 1 2 NM_005080_985-1003 13 2 2 2 1 1 3 3NM_005080_187-205 4 2 8 2 1 0 1 0 NM_005080_672-690 8 2 2 2 1 0 1 2NM_005080_771-789 3 2 10 2 1 0 6 1 NM_005080_1740-1758 1 1.2 5 2 1 3.2 12.2 NM_005080_1741-1759 1 1.2 2 1 3 3.2 1 2.2 NM_005080_662-680 1 1.2 21 1 2.4 2 1 NM_005080_1070-1088 1 1.2 6 2 4 2.2 14 2 NM_005080_631-649 11.2 2 0 2 2.2 1 1 NM_005080_647-665 2 1.2 2 2 2 2.2 1 2NM_005080_791-809 1 1.2 2 2.2 1 2.2 1 2.2 NM_005080_981-999 2 1.2 1 2 142.2 1 2 NM_005080_1068-1086 1 1.2 1 2 1 2 1 2 NM_005080_1391-1409 1 1.21 1 1 2 1 1 NM_005080_1426-1444 2 1.2 2 2.4 1 2 9 3 NM_005080_103-121 11.2 6 3 8 2 9 3 NM_005080_1457-1475 1 1.2 2 2.2 2 2 1 2NM_005080_1568-1586 2 1.2 1 2 5 2 10 2 NM_005080_1574-1592 1 1.2 13 3 72 2 2 NM_005080_1577-1595 1 1.2 1 1 5 2 3 1 NM_005080_1730-1748 2 1.2 11 4 2 3 1 NM_005080_1731-1749 4 1.2 1 1.2 4 2 3 1.2 NM_005080_1732-17502 1.2 3 2 3 2 5 2 NM_005080_293-311 2 1.2 4 2 3 2 5 2 NM_005080_350-3681 1.2 3 2.2 1 2 1 1.2 NM_005080_351-369 1 1.2 1 2.2 5 2 1 2.2NM_005080_630-648 1 1.2 2 2 1 2 2 2 NM_005080_657-675 2 1.2 1 1 2 2 1 1NM_005080_670-688 1 1.2 4 2 2 2 2 3 NM_005080_692-710 2 1.2 1 1 1 2 6 1NM_005080_778-796 1 1.2 8 3 4 2 2 2 NM_005080_790-808 1 1.2 8 2.2 1 2 33 NM_005080_970-988 1 1.2 2 2 6 2 2 2 NM_005080_1162-1180 1 1.2 7 3 31.2 1 2.2 NM_005080_1368-1386 1 1.2 3 2.8 1 1.2 5 3 NM_005080_1515-15331 1.2 1 2 2 1.2 2 2.2 NM_005080_1541-1559 1 1.2 4 2 1 1.2 1 2NM_005080_1542-1560 1 1.2 1 2 1 1.2 2 2 NM_005080_1571-1589 1 1.2 2 2 11.2 4 2 NM_005080_151-169 1 1.2 11 2 1 1.2 8 3 NM_005080_160-178 2 1.2 32 1 1.2 5 2 NM_005080_326-344 1 1.2 1 3.2 1 1.2 1 3 NM_005080_327-345 11.2 2 3.2 1 1.2 1 3 NM_005080_331-349 2 1.2 4 2 2 1.2 1 1NM_005080_424-442 1 1.2 1 2.2 1 1.2 2 2 NM_005080_483-501 3 1.2 1 1.2 31.2 1 1.2 NM_005080_579-597 2 1.2 1 2.2 2 1.2 1 2 NM_005080_745-763 11.2 1 2 1 1.2 1 2.2 NM_005080_746-764 1 1.2 2 2 1 1.2 1 2NM_005080_812-830 2 1.2 5 2 1 1.2 4 2 NM_005080_871-889 1 1.2 2 3 7 1.23 3 NM_005080_892-910 2 1.2 3 3 8 1.2 1 2 NM_005080_978-996 1 1.2 2 2 11.2 1 1.2 NM_005080_982-1000 1 1.2 4 2.8 8 1.2 4 2.8 NM_005080_257-275 11.2 2 1 1 1 3 1 NM_005080_364-382 2 1.2 7 2 2 1 3 1 NM_005080_816-834 11.2 2 2 2 1 2 2 NM_005080_884-902 1 1.2 6 2 1 1 1 2 NM_005080_925-943 11.2 6 2.2 4 1 1 2 NM_005080_1440-1458 1 1 2 2 1 2.8 5 2NM_005080_784-802 1 1 2 2 20 2.8 1 1 NM_005080_1593-1611 2 1 1 2 2 2.2 12 NM_005080_301-319 1 1 10 3 2 2.2 9 3 NM_005080_674-692 2 1 2 2.4 1 2.21 1.2 NM_005080_783-801 1 1 2 2 2 2.2 3 1 NM_005080_921-939 1 1 4 2 102.2 2 2 NM_005080_1226-1244 2 1 3 1 4 2 1 1 NM_005080_1283-1301 2 1 1 25 2 2 1.2 NM_005080_1416-1434 1 1 1 1 9 2 10 2 NM_005080_1420-1438 1 1 11 5 2 1 1 NM_005080_1488-1506 1 1 3 2 1 2 2 1 NM_005080_1492-1510 1 1 12.2 1 2 3 3 NM_005080_111-129 1 1 3 1 10 2 1 1 NM_005080_1639-1657 1 1 42 1 2 2 2 NM_005080_1685-1703 1 1 2 2 8 2 1 2 NM_005080_1733-1751 2 1 11 7 2 1 1 NM_005080_1734-1752 1 1 5 2 7 2 1 1 NM_005080_1737-1755 1 1 21 2 2 2 1 NM_005080_1756-1774 2 1 3 2 7 2 2 2 NM_005080_1757-1775 1 1 42 7 2 3 2 NM_005080_152-170 1 1 6 2 5 2 4 2 NM_005080_153-171 1 1 3 2 12 4 2 NM_005080_163-181 2 1 3 2 1 2 4 2 NM_005080_167-185 1 1 2 0 2 2 11 NM_005080_200-218 1 1 1 2 9 2 1 2 NM_005080_252-270 9 1 5 2 6 2 7 2NM_005080_255-273 2 1 1 1.2 3 2 1 1.2 NM_005080_260-278 1 1 1 1 34 2 1 0NM_005080_271-289 2 1 3 2 8 2 4 2 NM_005080_297-315 1 1 1 1.2 9 2 1 1.2NM_005080_300-318 1 1 2 2 1 2 1 2 NM_005080_335-353 2 1 2 1 4 2 1 1NM_005080_368-386 1 1 1 2 1 2 6 2 NM_005080_378-396 5 1 2 1 6 2 1 1NM_005080_379-397 5 1 4 2 7 2 3 2 NM_005080_380-398 4 1 4 2 5 2 1 1NM_005080_389-407 1 1 3 2 1 2 1 1 NM_005080_426-444 1 1 1 2 4 2 1 1NM_005080_427-445 1 1 4 1.2 3 2 1 1 NM_005080_485-503 2 1 1 1.2 12 2 1 1NM_005080_487-505 1 1 2 1 6 2 1 1 NM_005080_488-506 2 1 2 2 1 2 3 2NM_005080_511-529 1 1 1 1.2 4 2 21 2 NM_005080_526-544 3 1 1 2 1 2 5 2.2NM_005080_575-593 1 1 2 2 2 2 1 2 NM_005080_593-611 2 1 3 2.2 16 2 1 2NM_005080_595-613 1 1 8 2 4 2 4 2 NM_005080_654-672 2 1 3 2 3 2 2 2NM_005080_675-693 3 1 1 2 1 2 4 2.2 NM_005080_683-701 1 1 1 2 3 2 1 1NM_005080_684-702 1 1 2 2 3 2 4 2 NM_005080_693-711 2 1 8 1 3 2 1 1NM_005080_694-712 3 1 12 2 2 2 8 2 NM_005080_726-744 2 1 1 1.2 14 2 11.2 NM_005080_744-762 2 1 2 2 2 2 3 2 NM_005080_765-783 1 1 2 3 2 2 12.8 NM_005080_768-786 3 1 2 2 2 2 3 2 NM_005080_777-795 1 1 4 2 2 2 5 2NM_005080_802-820 1 1 2 1 7 2 3 2 NM_005080_877-895 1 1 2 2.2 5 2 2 1NM_005080_878-896 1 1 2 2.2 2 2 1 2 NM_005080_885-903 1 1 3 2 2 2 2 2NM_005080_886-904 1 1 3 2 2 2 2 2 NM_005080_966-984 1 1 2 2.2 2 2 1 2.4NM_005080_969-987 1 1 5 2 12 2 2 2 NM_005080_1245-1263 1 1 1 2 1 1.2 2 2NM_005080_1738-1756 1 1 9 2 2 1.2 1 1 NM_005080_194-212 1 1 1 1 1 1.2 21 NM_005080_209-227 1 1 1 1 1 1.2 1 1 NM_005080_269-287 2 1 21 2 3 1.217 2 NM_005080_902-920 1 1 1 1.2 5 1.2 1 2.2 NM_005080_50-68 2 1 8 1 11.2 8 1 NM_005080_1017-1035 1 1 1 2.2 1 1 4 3 NM_005080_1021-1039 2 1 12 1 1 1 2 NM_005080_1022-1040 2 1 1 1 1 1 2 2 NM_005080_1062-1080 2 1 32 3 1 1 2 NM_005080_1074-1092 1 1 1 2 2 1 2 2.2 NM_005080_1116-1134 5 12 2.2 2 1 12 3 NM_005080_1149-1167 1 1 1 2 1 1 10 3 NM_005080_1150-11682 1 1 2 8 1 1 1.2 NM_005080_1161-1179 1 1 1 2 1 1 1 2NM_005080_1223-1241 2 1 2 1 5 1 25 2 NM_005080_1280-1298 1 1 1 1 1 1 1 1NM_005080_1281-1299 1 1 1 1 1 1 3 1 NM_005080_1284-1302 4 1 1 1 1 1 1 1NM_005080_1286-1304 1 1 3 2 2 1 2 2 NM_005080_1288-1306 2 1 5 2 3 1 1 2NM_005080_1365-1383 1 1 1 2.2 1 1 10 3 NM_005080_1417-1435 2 1 4 2 1 1 52 NM_005080_1421-1439 1 1 2 2 1 1 1 2 NM_005080_1434-1452 3 1 1 2 1 1 12.2 NM_005080_1452-1470 1 1 4 2 1 1 4 2 NM_005080_105-123 1 1 1 1 2 1 32 NM_005080_1455-1473 1 1 5 2 2 1 3 2 NM_005080_112-130 1 1 2 1 1 1 11.2 NM_005080_113-131 2 1 3 1 2 1 1 1 NM_005080_1543-1561 3 1 3 2.2 2 11 2.2 NM_005080_1544-1562 2 1 6 3 2 1 1 2 NM_005080_1557-1575 1 1 6 2 41 6 1 NM_005080_115-133 2 1 1 0 1 1 1 1.2 NM_005080_1564-1582 1 1 3 1 41 4 1 NM_005080_1572-1590 1 1 3 2 1 1 4 2 NM_005080_1575-1593 1 1 5 2 11 4 2 NM_005080_1576-1594 1 1 1 2 1 1 1 2 NM_005080_117-135 4 1 3 1 14 110 1 NM_005080_1582-1600 1 1 9 2 1 1 1 1 NM_005080_1587-1605 1 1 5 2 3 112 2 NM_005080_118-136 8 1 5 1 10 1 3 1 NM_005080_119-137 7 1 2 1 4 1 11 NM_005080_120-138 6 1 47 2 7 1 35 2 NM_005080_124-142 6 1 1 0 1 1 1 0NM_005080_126-144 1 1 3 1 2 1 1 1 NM_005080_1676-1694 1 1 2 2 1 1 5 2NM_005080_127-145 7 1 2 1 3 1 1 1 NM_005080_129-147 3 1 18 2 2 1 2 1NM_005080_130-148 4 1 7 1 1 1 5 1 NM_005080_131-149 1 1 1 0 1 1 6 1NM_005080_1720-1738 1 1 1 3 4 1 1 3 NM_005080_1724-1742 1 1 2 2 2 1 2 2NM_005080_132-150 3 1 3 1 1 1 3 1 NM_005080_133-151 5 1 1 1 3 1 3 1NM_005080_134-152 2 1 1 1.2 1 1 1 1 NM_005080_136-154 3 1 1 1 2 1 7 1NM_005080_1777-1795 1 1 1 1 1 1 4 2 NM_005080_137-155 4 1 4 1 4 1 7 1NM_005080_139-157 10 1 1 1.2 2 1 7 2 NM_005080_140-158 1 1 1 1.2 2 1 11.2 NM_005080_141-159 7 1 1 0 7 1 1 0 NM_005080_142-160 4 1 1 0 1 1 1 0NM_005080_143-161 6 1 1 0 2 1 3 1 NM_005080_144-162 1 1 5 1 4 1 9 1NM_005080_161-179 2 1 4 2 1 1 1 2 NM_005080_162-180 4 1 6 2 2 1 6 3NM_005080_164-182 2 1 2 2 1 1 4 2 NM_005080_165-183 1 1 7 2 4 1 1 1NM_005080_166-184 3 1 2 1 2 1 7 1 NM_005080_201-219 4 1 4 2 1 1 1 2NM_005080_202-220 5 1 3 1 4 1 1 1 NM_005080_203-221 3 1 6 1 3 1 1 1NM_005080_204-222 3 1 9 1 2 1 1 1 NM_005080_208-226 3 1 2 1 2 1 4 1NM_005080_212-230 2 1 2 1 1 1 5 2 NM_005080_248-266 4 1 1 1 5 1 11 1NM_005080_251-269 1 1 9 2 2 1 1 1 NM_005080_258-276 2 1 2 2 1 1 12 2NM_005080_262-280 2 1 4 2 1 1 1 0 NM_005080_265-283 2 1 2 2 3 1 4 2.2NM_005080_266-284 2 1 7 2 2 1 1 1 NM_005080_267-285 4 1 2 1 1 1 1 1NM_005080_268-286 3 1 6 2 1 1 1 1 NM_005080_270-288 3 1 4 2 1 1 6 2NM_005080_272-290 2 1 1 2 1 1 2 2 NM_005080_273-291 2 1 4 1 3 1 1 2NM_005080_277-295 4 1 3 1 2 1 1 1 NM_005080_328-346 1 1 2 2 1 1 8 3NM_005080_329-347 1 1 1 2 1 1 11 3 NM_005080_334-352 1 1 4 1 1 1 2 1NM_005080_336-354 1 1 1 1 1 1 1 1 NM_005080_337-355 4 1 1 1 2 1 1 1NM_005080_338-356 5 1 1 1 3 1 1 1.2 NM_005080_356-374 1 1 1 1 1 1 1 2NM_005080_357-375 2 1 2 2 2 1 2 2 NM_005080_359-377 1 1 1 2 1 1 2 2.8NM_005080_360-378 1 1 1 2 1 1 1 2 NM_005080_362-380 4 1 1 1 4 1 1 1NM_005080_367-385 1 1 3 2 1 1 2 2 NM_005080_382-400 6 1 8 2.2 2 1 5 1.2NM_005080_386-404 1 1 2 2 1 1 2 2 NM_005080_401-419 2 1 3 1 1 1 1 1NM_005080_458-476 3 1 1 2 1 1 3 2 NM_005080_484-502 3 1 6 2 2 1 1 1NM_005080_489-507 2 1 1 2 1 1 1 1.2 NM_005080_574-592 1 1 3 2 5 1 4 2.2NM_005080_594-612 6 1 7 2 13 1 12 2 NM_005080_604-622 4 1 2 2 3 1 3 2NM_005080_627-645 2 1 2 1 3 1 3 1 NM_005080_635-653 1 1 4 2 3 1 2 2NM_005080_636-654 1 1 8 1.2 2 1 1 1.2 NM_005080_666-684 2 1 4 2.2 7 1 93 NM_005080_667-685 1 1 1 2 1 1 1 2 NM_005080_669-687 1 1 8 3 1 1 4 3NM_005080_681-699 2 1 4 2 1 1 2 2 NM_005080_690-708 5 1 5 2 1 1 6 2NM_005080_718-736 4 1 1 1.2 5 1 1 1 NM_005080_722-740 3 1 1 1 3 1 2 1NM_005080_723-741 3 1 1 1 3 1 1 1 NM_005080_724-742 6 1 2 1 4 1 3 0NM_005080_725-743 5 1 2 1 2 1 7 1 NM_005080_727-745 1 1 1 1 1 1 2 1.2NM_005080_728-746 1 1 2 1 3 1 4 1 NM_005080_739-757 1 1 5 2.2 4 1 1 2.2NM_005080_747-765 1 1 1 2 7 1 8 3 NM_005080_763-781 1 1 2 2 6 1 1 2NM_005080_764-782 3 1 1 2.8 3 1 1 2.2 NM_005080_766-784 1 1 13 2 1 1 1 1NM_005080_770-788 1 1 2 1 1 1 4 2 NM_005080_774-792 2 1 2 1 4 1 1 1NM_005080_780-798 5 1 1 1 20 1 1 1 NM_005080_781-799 5 1 4 2 20 1 8 2NM_005080_805-823 1 1 1 1 1 1 3 1 NM_005080_44-62 30 1 4 2 42 1 5 2.8NM_005080_45-63 2 1 3 0 5 1 5 0 NM_005080_868-886 1 1 1 2.2 1 1 16 3NM_005080_875-893 1 1 1 3.2 1 1 3 3.2 NM_005080_47-65 5 1 6 2 10 1 1 1NM_005080_879-897 1 1 3 2 2 1 1 1 NM_005080_880-898 1 1 3 2 1 1 3 2NM_005080_881-899 1 1 15 2 1 1 18 2 NM_005080_882-900 1 1 2 2 1 1 1 2NM_005080_883-901 1 1 1 2 4 1 1 2 NM_005080_49-67 3 1 1 0 1 1 13 1NM_005080_914-932 1 1 1 3 1 1 2 4 NM_005080_915-933 1 1 1 2 1 1 4 3NM_005080_926-944 10 1 1 2 7 1 1 2 NM_005080_945-963 2 1 3 2 3 1 7 2NM_005080_958-976 2 1 1 0 1 1 1 1 NM_005080_959-977 2 1 1 0 1 1 1 2NM_005080_962-980 1 1 1 1 1 1 1 1 NM_005080_975-993 1 1 4 2 1 1 2 2NM_005080_983-1001 1 1 3 1 1 1 1 1 NM_005080_128-146 2 1 2 1 1 0 8 2NM_005080_249-267 1 1 1 1 1 0 11 1 NM_005080_697-715 1 1 2 2 1 0 1 2.2NM_005080_729-747 3 1 2 1 1 0 9 1.2 NM_005080_776-794 1 0 4 1.2 1 2.2 21.2 NM_005080_803-821 1 0 11 2 2 2.2 4 2 NM_005080_254-272 9 0 6 2 1 2 22 NM_005080_383-401 2 0 2 2 2 2 7 2 NM_005080_116-134 2 0 7 1 14 1 6 1NM_005080_123-141 1 0 1 1 2 1 13 2 NM_005080_125-143 1 0 1 0 2 1 1 0NM_005080_135-153 2 0 10 2 1 1 1 0 NM_005080_253-271 9 0 13 2 2 1 11 2NM_005080_274-292 1 0 3 1 2 1 2 2 NM_005080_655-673 2 0 3 2.8 1 1 1 2NM_005080_775-793 1 0 2 1.2 1 1 1 1 NM_005080_46-64 1 0 3 1 15 1 9 1NM_005080_1456-1474 1 0 4 2 2 0 1 1.2 NM_005080_1545-1563 1 0 9 3 1 0 11 NM_005080_1558-1576 1 0 2 2 3 0 8 2 NM_005080_121-139 1 0 1 0 1 0 48 2NM_005080_122-140 1 0 1 1 1 0 13 2 NM_005080_247-265 1 0 1 1 1 0 1 1NM_005080_275-293 1 0 4 1 1 0 2 1 NM_005080_276-294 1 0 1 1 1 0 1 1NM_005080_358-376 1 0 8 2.2 1 0 6 2.2 NM_005080_387-405 1 0 2 2 1 0 3 2NM_005080_628-646 2 0 1 0 2 0 3 1 NM_005080_656-674 2 0 1 1 1 0 1 1NM_005080_719-737 1 0 6 2 1 0 6 2 NM_005080_720-738 2 0 4 1 3 0 1 1NM_005080_721-739 1 0 1 1.2 1 0 9 2 NM_005080_782-800 5 0 3 2 20 0 12 2NM_005080_867-885 2 0 5 2 2 0 1 2.2 NM_005080_48-66 2 0 3 1 1 0 1 0NM_005080_963-981 1 0 1 1 1 0 5 2 Gene XBP-1 reference transcriptNM_005080 (human XBP-1 mRNA, FIG. 2) Notes 19 mers found in both humanand rhesus

TABLE 11 XBP-1 mouse/Rhesus siRNAs Target sequence on rhesus mRNA SEQtranscript ID SEQ ID 5′ to 3′ sense (5′-3′) NO: antisense (5′-3′) NO:NM_013842_369-387 AGAAAACUCACGGCCUUGU 2119 ACAAGGCCGUGAGUUUUCU 2120NM_013842_237-255 AACUGAAAAACAGAGUAGC 321 GCUACUCUGUUUUUCAGUU 322NM_013842_491-509 GGGUCUGCUGAGUCCGCAG 1693 CUGCGGACUCAGCAGACCC 1694NM_013842_917-935 AUCACCCUGAAUUCAUUGU 197 ACAAUGAAUUCAGGGUGAU 198NM_013842_923-941 CUGAAUUCAUUGUCUCAGU 2037 ACUGAGACAAUGAAUUCAG 2038NM_013842_702-720 CCCAGAGGUCUACCCAGAA 1181 UUCUGGGUAGACCUCUGGG 1182NM_013842_926-944 AAUUCAUUGUCUCAGUGAA 1349 UUCACUGAGACAAUGAAUU 1350NM_013842_391-409 UGAGAACCAGGAGUUAAGA 1035 UCUUAACUCCUGGUUCUCA 1036NM_013842_775-793 AAGCUGGAAGCCAUUAAUG 1249 CAUUAAUGGCUUCCAGCUU 1250NM_013842_1150-1168 CCCCAGCUGAUUAGUGUCU 123 AGACACUAAUCAGCUGGGG 124NM_013842_776-794 AGCUGGAAGCCAUUAAUGA 1251 UCAUUAAUGGCUUCCAGCU 1252NM_013842_921-939 CCCUGAAUUCAUUGUCUCA 1343 UGAGACAAUGAAUUCAGGG 1344NM_013842_777-795 GCUGGAAGCCAUUAAUGAA 1585 UUCAUUAAUGGCUUCCAGC 1586NM_013842_539-557 GUGCAGGCCCAGUUGUCAC 1951 GUGACAACUGGGCCUGCAC 1952NM_013842_731-749 CCUUACCAGCCUCCCUUUC 1995 GAAAGGGAGGCUGGUAAGG 1996NM_013842_924-942 UGAAUUCAUUGUCUCAGUG 2039 CACUGAGACAAUGAAUUCA 2040NM_013842_1151-1169 CCCAGCUGAUUAGUGUCUA 43 UAGACACUAAUCAGCUGGG 44NM_013842_1152-1170 CCAGCUGAUUAGUGUCUAA 125 UUAGACACUAAUCAGCUGG 126NM_013842_1718-1736 ACUAUGUAAAUGCUUGAUG 479 CAUCAAGCAUUUACAUAGU 480NM_013842_368-386 GAGAAAACUCACGGCCUUG 2121 CAAGGCCGUGAGUUUUCUC 2122NM_013842_489-507 CCGGGUCUGCUGAGUCCGC 499 GCGGACUCAGCAGACCCGG 500NM_013842_238-256 ACUGAAAAACAGAGUAGCA 289 UGCUACUCUGUUUUUCAGU 290NM_013842_240-258 UGAAAAACAGAGUAGCAGC 529 GCUGCUACUCUGUUUUUCA 530NM_013842_390-408 UUGAGAACCAGGAGUUAAG 329 CUUAACUCCUGGUUCUCAA 330NM_013842_487-505 GGCCGGGUCUGCUGAGUCC 569 GGACUCAGCAGACCCGGCC 570NM_013842_741-759 CUCCCUUUCUCUGUCAGUG 2055 CACUGACAGAGAAAGGGAG 2056NM_013842_918-936 UCACCCUGAAUUCAUUGUC 157 GACAAUGAAUUCAGGGUGA 158NM_013842_919-937 CACCCUGAAUUCAUUGUCU 343 AGACAAUGAAUUCAGGGUG 344NM_013842_1130-1148 CUUUUGCCAAUGAACUUUU 2123 AAAAGUUCAUUGGCAAAAG 2124NM_013842_1712-1730 AAAUUUACUAUGUAAAUGC 845 GCAUUUACAUAGUAAAUUU 846NM_013842_1714-1732 AUUUACUAUGUAAAUGCUU 847 AAGCAUUUACAUAGUAAAU 848NM_013842_1717-1735 UACUAUGUAAAUGCUUGAU 851 AUCAAGCAUUUACAUAGUA 852NM_013842_1719-1737 CUAUGUAAAUGCUUGAUGG 853 CCAUCAAGCAUUUACAUAG 854NM_013842_1775-1793 CCAUUUAUUUAAAACUACC 379 GGUAGUUUUAAAUAAAUGG 380NM_013842_1776-1794 CAUUUAUUUAAAACUACCC 381 GGGUAGUUUUAAAUAAAUG 382NM_013842_239-257 CUGAAAAACAGAGUAGCAG 383 CUGCUACUCUGUUUUUCAG 384NM_013842_347-365 CUAGAAAAUCAGCUUUUAC 1013 GUAAAAGCUGAUUUUCUAG 1014NM_013842_348-366 UAGAAAAUCAGCUUUUACG 1679 CGUAAAAGCUGAUUUUCUA 1680NM_013842_485-503 GUGGCCGGGUCUGCUGAGU 1063 ACUCAGCAGACCCGGCCAC 1064NM_013842_486-504 UGGCCGGGUCUGCUGAGUC 1065 GACUCAGCAGACCCGGCCA 1066NM_013842_488-506 GCCGGGUCUGCUGAGUCCG 1067 CGGACUCAGCAGACCCGGC 1068NM_013842_540-558 UGCAGGCCCAGUUGUCACC 1695 GGUGACAACUGGGCCUGCA 1696NM_013842_703-721 CCAGAGGUCUACCCAGAAG 1183 CUUCUGGGUAGACCUCUGG 1184NM_013842_705-723 AGAGGUCUACCCAGAAGGA 1185 UCCUUCUGGGUAGACCUCU 1186NM_013842_730-748 UCCUUACCAGCCUCCCUUU 1717 AAAGGGAGGCUGGUAAGGA 1718NM_013842_742-760 UCCCUUUCUCUGUCAGUGG 1721 CCACUGACAGAGAAAGGGA 1722NM_013842_744-762 CCUUUCUCUGUCAGUGGGG 1221 CCCCACUGACAGAGAAAGG 1222NM_013842_767-785 CAUCAGCCAAGCUGGAAGC 1723 GCUUCCAGCUUGGCUGAUG 1724NM_013842_771-789 AGCCAAGCUGGAAGCCAUU 1241 AAUGGCUUCCAGCUUGGCU 1242NM_013842_916-934 GAUCACCCUGAAUUCAUUG 195 CAAUGAAUUCAGGGUGAUC 196NM_013842_920-938 ACCCUGAAUUCAUUGUCUC 1341 GAGACAAUGAAUUCAGGGU 1342NM_013842_922-940 CCUGAAUUCAUUGUCUCAG 1345 CUGAGACAAUGAAUUCAGG 1346NM_013842_925-943 GAAUUCAUUGUCUCAGUGA 1347 UCACUGAGACAAUGAAUUC 1348NM_013842_1720-1738 UAUGUAAAUGCUUGAUGGA 1841 UCCAUCAAGCAUUUACAUA 1842NM_013842_232-250 GAGGAAACUGAAAAACAGA 1911 UCUGUUUUUCAGUUUCCUC 1912NM_013842_236-254 AAACUGAAAAACAGAGUAG 1913 CUACUCUGUUUUUCAGUUU 1914NM_013842_728-746 GUUCCUUACCAGCCUCCCU 1991 AGGGAGGCUGGUAAGGAAC 1992NM_013842_729-747 UUCCUUACCAGCCUCCCUU 1993 AAGGGAGGCUGGUAAGGAA 1994NM_013842_745-763 CUUUCUCUGUCAGUGGGGA 2001 UCCCCACUGACAGAGAAAG 2002NM_013842_766-784 UCAUCAGCCAAGCUGGAAG 1473 CUUCCAGCUUGGCUGAUGA 1474NM_013842_927-945 AUUCAUUGUCUCAGUGAAG 2041 CUUCACUGAGACAAUGAAU 2042NM_013842_234-252 GGAAACUGAAAAACAGAGU 2093 ACUCUGUUUUUCAGUUUCC 2094NM_013842_235-253 GAAACUGAAAAACAGAGUA 2095 UACUCUGUUUUUCAGUUUC 2096NM_013842_346-364 GCUAGAAAAUCAGCUUUUA 2099 UAAAAGCUGAUUUUCUAGC 2100NM_013842_490-508 CGGGUCUGCUGAGUCCGCA 501 UGCGGACUCAGCAGACCCG 502NM_013842_700-718 CUCCCAGAGGUCUACCCAG 91 CUGGGUAGACCUCUGGGAG 92NM_013842_1715-1733 UUUACUAUGUAAAUGCUUG 849 CAAGCAUUUACAUAGUAAA 850NM_013842_734-752 UACCAGCCUCCCUUUCUCU 1217 AGAGAAAGGGAGGCUGGUA 1218NM_013842_773-791 CCAAGCUGGAAGCCAUUAA 1245 UUAAUGGCUUCCAGCUUGG 1246NM_013842_778-796 CUGGAAGCCAUUAAUGAAC 1253 GUUCAUUAAUGGCUUCCAG 1254NM_013842_779-797 UGGAAGCCAUUAAUGAACU 1255 AGUUCAUUAAUGGCUUCCA 1256NM_013842_1774-1792 UCCAUUUAUUUAAAACUAC 1853 GUAGUUUUAAAUAAAUGGA 1854NM_013842_704-722 CAGAGGUCUACCCAGAAGG 1987 CCUUCUGGGUAGACCUCUG 1988NM_013842_1716-1734 UUACUAUGUAAAUGCUUGA 477 UCAAGCAUUUACAUAGUAA 478NM_013842_1713-1731 AAUUUACUAUGUAAAUGCU 315 AGCAUUUACAUAGUAAAUU 316NM_013842_768-786 AUCAGCCAAGCUGGAAGCC 2057 GGCUUCCAGCUUGGCUGAU 2058NM_013842_1129-1147 ACUUUUGCCAAUGAACUUU 2125 AAAGUUCAUUGGCAAAAGU 2126NM_013842_389-407 GUUGAGAACCAGGAGUUAA 245 UUAACUCCUGGUUCUCAAC 246NM_013842_701-719 UCCCAGAGGUCUACCCAGA 1179 UCUGGGUAGACCUCUGGGA 1180NM_013842_706-724 GAGGUCUACCCAGAAGGAC 1187 GUCCUUCUGGGUAGACCUC 1188NM_013842_707-725 AGGUCUACCCAGAAGGACC 1189 GGUCCUUCUGGGUAGACCU 1190NM_013842_727-745 AGUUCCUUACCAGCCUCCC 1213 GGGAGGCUGGUAAGGAACU 1214NM_013842_733-751 UUACCAGCCUCCCUUUCUC 1719 GAGAAAGGGAGGCUGGUAA 1720NM_013842_736-754 CCAGCCUCCCUUUCUCUGU 1493 ACAGAGAAAGGGAGGCUGG 1494NM_013842_738-756 AGCCUCCCUUUCUCUGUCA 1219 UGACAGAGAAAGGGAGGCU 1220NM_013842_743-761 CCCUUUCUCUGUCAGUGGG 1547 CCCACUGACAGAGAAAGGG 1548NM_013842_769-787 UCAGCCAAGCUGGAAGCCA 1239 UGGCUUCCAGCUUGGCUGA 1240NM_013842_772-790 GCCAAGCUGGAAGCCAUUA 1243 UAAUGGCUUCCAGCUUGGC 1244NM_013842_774-792 CAAGCUGGAAGCCAUUAAU 1247 AUUAAUGGCUUCCAGCUUG 1248NM_013842_231-249 GGAGGAAACUGAAAAACAG 1909 CUGUUUUUCAGUUUCCUCC 1910NM_013842_233-251 AGGAAACUGAAAAACAGAG 2073 CUCUGUUUUUCAGUUUCCU 2074NM_013842_735-753 ACCAGCCUCCCUUUCUCUG 1997 CAGAGAAAGGGAGGCUGGU 1998NM_013842_737-755 CAGCCUCCCUUUCUCUGUC 1471 GACAGAGAAAGGGAGGCUG 1472NM_013842_739-757 GCCUCCCUUUCUCUGUCAG 1999 CUGACAGAGAAAGGGAGGC 2000NM_013842_740-758 CCUCCCUUUCUCUGUCAGU 2077 ACUGACAGAGAAAGGGAGG 2078NM_013842_746-764 UUUCUCUGUCAGUGGGGAC 2003 GUCCCCACUGACAGAGAAA 2004NM_013842_770-788 CAGCCAAGCUGGAAGCCAU 2005 AUGGCUUCCAGCUUGGCUG 2006NM_013842_26-44 GCUAUGGUGGUGGUGGCAG 2079 CUGCCACCACCACCAUAGC 2080NM_013842_27-45 CUAUGGUGGUGGUGGCAGC 2015 GCUGCCACCACCACCAUAG 2016NM_013842_732-750 CUUACCAGCCUCCCUUUCU 1215 AGAAAGGGAGGCUGGUAAG 1216 GeneXBP-1 reference transcript NM_013842 (Mus musculis XPB1 mRNA, FIG. 3)Notes 100 siRNA sequences common to both mouse and rhesus

TABLE 12 XBP-1 mouse/Rhesus siRNAs with 3′dinucleotide overhangs Targetsequence on sense (5′-3′) SEQ SEQ rhesus mRNA with 3′ dinucleotide IDantisense (5′-3′) ID transcript 5′ to 3′ overhang NO: with3′ dinucleotide overhang NO: NM_013842_369-387 AGAAAACUCACGGCCUUGUNN4321 ACAAGGCCGUGAGUUUUCUNN 4322 NM_013842_237-255 AACUGAAAAACAGAGUAGCNN2523 GCUACUCUGUUUUUCAGUUNN 2524 NM_013842_491-509 GGGUCUGCUGAGUCCGCAGNN3895 CUGCGGACUCAGCAGACCCNN 3896 NM_013842_917-935 AUCACCCUGAAUUCAUUGUNN2399 ACAAUGAAUUCAGGGUGAUNN 2400 NM_013842_923-941 CUGAAUUCAUUGUCUCAGUNN4239 ACUGAGACAAUGAAUUCAGNN 4240 NM_013842_702-720 CCCAGAGGUCUACCCAGAANN3383 UUCUGGGUAGACCUCUGGGNN 3384 NM_013842_926-944 AAUUCAUUGUCUCAGUGAANN3551 UUCACUGAGACAAUGAAUUNN 3552 NM_013842_391-409 UGAGAACCAGGAGUUAAGANN3237 UCUUAACUCCUGGUUCUCANN 3238 NM_013842_775-793 AAGCUGGAAGCCAUUAAUGNN3451 CAUUAAUGGCUUCCAGCUUNN 3452 NM_013842_1150-1168CCCCAGCUGAUUAGUGUCUNN 2325 AGACACUAAUCAGCUGGGGNN 2326 NM_013842_776-794AGCUGGAAGCCAUUAAUGANN 3453 UCAUUAAUGGCUUCCAGCUNN 3454 NM_013842_921-939CCCUGAAUUCAUUGUCUCANN 3545 UGAGACAAUGAAUUCAGGGNN 3546 NM_013842_777-795GCUGGAAGCCAUUAAUGAANN 3787 UUCAUUAAUGGCUUCCAGCNN 3788 NM_013842_539-557GUGCAGGCCCAGUUGUCACNN 4153 GUGACAACUGGGCCUGCACNN 4154 NM_013842_731-749CCUUACCAGCCUCCCUUUCNN 4197 GAAAGGGAGGCUGGUAAGGNN 4198 NM_013842_924-942UGAAUUCAUUGUCUCAGUGNN 4241 CACUGAGACAAUGAAUUCANN 4242NM_013842_1151-1169 CCCAGCUGAUUAGUGUCUANN 2245 UAGACACUAAUCAGCUGGGNN2246 NM_013842_1152-1170 CCAGCUGAUUAGUGUCUAANN 2327UUAGACACUAAUCAGCUGGNN 2328 NM_013842_1718-1736 ACUAUGUAAAUGCUUGAUGNN2681 CAUCAAGCAUUUACAUAGUNN 2682 NM_013842_368-386 GAGAAAACUCACGGCCUUGNN4323 CAAGGCCGUGAGUUUUCUCNN 4324 NM_013842_489-507 CCGGGUCUGCUGAGUCCGCNN2701 GCGGACUCAGCAGACCCGGNN 2702 NM_013842_238-256 ACUGAAAAACAGAGUAGCANN2491 UGCUACUCUGUUUUUCAGUNN 2492 NM_013842_240-258 UGAAAAACAGAGUAGCAGCNN2731 GCUGCUACUCUGUUUUUCANN 2732 NM_013842_390-408 UUGAGAACCAGGAGUUAAGNN2531 CUUAACUCCUGGUUCUCAANN 2532 NM_013842_487-505 GGCCGGGUCUGCUGAGUCCNN2771 GGACUCAGCAGACCCGGCCNN 2772 NM_013842_741-759 CUCCCUUUCUCUGUCAGUGNN4257 CACUGACAGAGAAAGGGAGNN 4258 NM_013842_918-936 UCACCCUGAAUUCAUUGUCNN2359 GACAAUGAAUUCAGGGUGANN 2360 NM_013842_919-937 CACCCUGAAUUCAUUGUCUNN2545 AGACAAUGAAUUCAGGGUGNN 2546 NM_013842_1130-1148CUUUUGCCAAUGAACUUUUNN 4325 AAAAGUUCAUUGGCAAAAGNN 4326NM_013842_1712-1730 AAAUUUACUAUGUAAAUGCNN 3047 GCAUUUACAUAGUAAAUUUNN3048 NM_013842_1714-1732 AUUUACUAUGUAAAUGCUUNN 3049AAGCAUUUACAUAGUAAAUNN 3050 NM_013842_1717-1735 UACUAUGUAAAUGCUUGAUNN3053 AUCAAGCAUUUACAUAGUANN 3054 NM_013842_1719-1737CUAUGUAAAUGCUUGAUGGNN 3055 CCAUCAAGCAUUUACAUAGNN 3056NM_013842_1775-1793 CCAUUUAUUUAAAACUACCNN 2581 GGUAGUUUUAAAUAAAUGGNN2582 NM_013842_1776-1794 CAUUUAUUUAAAACUACCCNN 2583GGGUAGUUUUAAAUAAAUGNN 2584 NM_013842_239-257 CUGAAAAACAGAGUAGCAGNN 2585CUGCUACUCUGUUUUUCAGNN 2586 NM_013842_347-365 CUAGAAAAUCAGCUUUUACNN 3215GUAAAAGCUGAUUUUCUAGNN 3216 NM_013842_348-366 UAGAAAAUCAGCUUUUACGNN 3881CGUAAAAGCUGAUUUUCUANN 3882 NM_013842_485-503 GUGGCCGGGUCUGCUGAGUNN 3265ACUCAGCAGACCCGGCCACNN 3266 NM_013842_486-504 UGGCCGGGUCUGCUGAGUCNN 3267GACUCAGCAGACCCGGCCANN 3268 NM_013842_488-506 GCCGGGUCUGCUGAGUCCGNN 3269CGGACUCAGCAGACCCGGCNN 3270 NM_013842_540-558 UGCAGGCCCAGUUGUCACCNN 3897GGUGACAACUGGGCCUGCANN 3898 NM_013842_703-721 CCAGAGGUCUACCCAGAAGNN 3385CUUCUGGGUAGACCUCUGGNN 3386 NM_013842_705-723 AGAGGUCUACCCAGAAGGANN 3387UCCUUCUGGGUAGACCUCUNN 3388 NM_013842_730-748 UCCUUACCAGCCUCCCUUUNN 3919AAAGGGAGGCUGGUAAGGANN 3920 NM_013842_742-760 UCCCUUUCUCUGUCAGUGGNN 3923CCACUGACAGAGAAAGGGANN 3924 NM_013842_744-762 CCUUUCUCUGUCAGUGGGGNN 3423CCCCACUGACAGAGAAAGGNN 3424 NM_013842_767-785 CAUCAGCCAAGCUGGAAGCNN 3925GCUUCCAGCUUGGCUGAUGNN 3926 NM_013842_771-789 AGCCAAGCUGGAAGCCAUUNN 3443AAUGGCUUCCAGCUUGGCUNN 3444 NM_013842_916-934 GAUCACCCUGAAUUCAUUGNN 2397CAAUGAAUUCAGGGUGAUCNN 2398 NM_013842_920-938 ACCCUGAAUUCAUUGUCUCNN 3543GAGACAAUGAAUUCAGGGUNN 3544 NM_013842_922-940 CCUGAAUUCAUUGUCUCAGNN 3547CUGAGACAAUGAAUUCAGGNN 3548 NM_013842_925-943 GAAUUCAUUGUCUCAGUGANN 3549UCACUGAGACAAUGAAUUCNN 3550 NM_013842_1720-1738 UAUGUAAAUGCUUGAUGGANN4043 UCCAUCAAGCAUUUACAUANN 4044 NM_013842_232-250 GAGGAAACUGAAAAACAGANN4113 UCUGUUUUUCAGUUUCCUCNN 4114 NM_013842_236-254 AAACUGAAAAACAGAGUAGNN4115 CUACUCUGUUUUUCAGUUUNN 4116 NM_013842_728-746 GUUCCUUACCAGCCUCCCUNN4193 AGGGAGGCUGGUAAGGAACNN 4194 NM_013842_729-747 UUCCUUACCAGCCUCCCUUNN4195 AAGGGAGGCUGGUAAGGAANN 4196 NM_013842_745-763 CUUUCUCUGUCAGUGGGGANN4203 UCCCCACUGACAGAGAAAGNN 4204 NM_013842_766-784 UCAUCAGCCAAGCUGGAAGNN3675 CUUCCAGCUUGGCUGAUGANN 3676 NM_013842_927-945 AUUCAUUGUCUCAGUGAAGNN4243 CUUCACUGAGACAAUGAAUNN 4244 NM_013842_234-252 GGAAACUGAAAAACAGAGUNN4295 ACUCUGUUUUUCAGUUUCCNN 4296 NM_013842_235-253 GAAACUGAAAAACAGAGUANN4297 UACUCUGUUUUUCAGUUUCNN 4298 NM_013842_346-364 GCUAGAAAAUCAGCUUUUANN4301 UAAAAGCUGAUUUUCUAGCNN 4302 NM_013842_490-508 CGGGUCUGCUGAGUCCGCANN2703 UGCGGACUCAGCAGACCCGNN 2704 NM_013842_700-718 CUCCCAGAGGUCUACCCAGNN2293 CUGGGUAGACCUCUGGGAGNN 2294 NM_013842_1715-1733UUUACUAUGUAAAUGCUUGNN 3051 CAAGCAUUUACAUAGUAAANN 3052 NM_013842_734-752UACCAGCCUCCCUUUCUCUNN 3419 AGAGAAAGGGAGGCUGGUANN 3420 NM_013842_773-791CCAAGCUGGAAGCCAUUAANN 3447 UUAAUGGCUUCCAGCUUGGNN 3448 NM_013842_778-796CUGGAAGCCAUUAAUGAACNN 3455 GUUCAUUAAUGGCUUCCAGNN 3456 NM_013842_779-797UGGAAGCCAUUAAUGAACUNN 3457 AGUUCAUUAAUGGCUUCCANN 3458NM_013842_1774-1792 UCCAUUUAUUUAAAACUACNN 4055 GUAGUUUUAAAUAAAUGGANN4056 NM_013842_704-722 CAGAGGUCUACCCAGAAGGNN 4189 CCUUCUGGGUAGACCUCUGNN4190 NM_013842_1716-1734 UUACUAUGUAAAUGCUUGANN 2679UCAAGCAUUUACAUAGUAANN 2680 NM_013842_1713-1731 AAUUUACUAUGUAAAUGCUNN2517 AGCAUUUACAUAGUAAAUUNN 2518 NM_013842_768-786 AUCAGCCAAGCUGGAAGCCNN4259 GGCUUCCAGCUUGGCUGAUNN 4260 NM_013842_1129-1147ACUUUUGCCAAUGAACUUUNN 4327 AAAGUUCAUUGGCAAAAGUNN 4328 NM_013842_389-407GUUGAGAACCAGGAGUUAANN 2447 UUAACUCCUGGUUCUCAACNN 2448 NM_013842_701-719UCCCAGAGGUCUACCCAGANN 3381 UCUGGGUAGACCUCUGGGANN 3382 NM_013842_706-724GAGGUCUACCCAGAAGGACNN 3389 GUCCUUCUGGGUAGACCUCNN 3390 NM_013842_707-725AGGUCUACCCAGAAGGACCNN 3391 GGUCCUUCUGGGUAGACCUNN 3392 NM_013842_727-745AGUUCCUUACCAGCCUCCCNN 3415 GGGAGGCUGGUAAGGAACUNN 3416 NM_013842_733-751UUACCAGCCUCCCUUUCUCNN 3921 GAGAAAGGGAGGCUGGUAANN 3922 NM_013842_736-754CCAGCCUCCCUUUCUCUGUNN 3695 ACAGAGAAAGGGAGGCUGGNN 3696 NM_013842_738-756AGCCUCCCUUUCUCUGUCANN 3421 UGACAGAGAAAGGGAGGCUNN 3422 NM_013842_743-761CCCUUUCUCUGUCAGUGGGNN 3749 CCCACUGACAGAGAAAGGGNN 3750 NM_013842_769-787UCAGCCAAGCUGGAAGCCANN 3441 UGGCUUCCAGCUUGGCUGANN 3442 NM_013842_772-790GCCAAGCUGGAAGCCAUUANN 3445 UAAUGGCUUCCAGCUUGGCNN 3446 NM_013842_774-792CAAGCUGGAAGCCAUUAAUNN 3449 AUUAAUGGCUUCCAGCUUGNN 3450 NM_013842_231-249GGAGGAAACUGAAAAACAGNN 4111 CUGUUUUUCAGUUUCCUCCNN 4112 NM_013842_233-251AGGAAACUGAAAAACAGAGNN 4275 CUCUGUUUUUCAGUUUCCUNN 4276 NM_013842_735-753ACCAGCCUCCCUUUCUCUGNN 4199 CAGAGAAAGGGAGGCUGGUNN 4200 NM_013842_737-755CAGCCUCCCUUUCUCUGUCNN 3673 GACAGAGAAAGGGAGGCUGNN 3674 NM_013842_739-757GCCUCCCUUUCUCUGUCAGNN 4201 CUGACAGAGAAAGGGAGGCNN 4202 NM_013842_740-758CCUCCCUUUCUCUGUCAGUNN 4279 ACUGACAGAGAAAGGGAGGNN 4280 NM_013842_746-764UUUCUCUGUCAGUGGGGACNN 4205 GUCCCCACUGACAGAGAAANN 4206 NM_013842_770-788CAGCCAAGCUGGAAGCCAUNN 4207 AUGGCUUCCAGCUUGGCUGNN 4208 NM_013842_26-44GCUAUGGUGGUGGUGGCAGNN 4281 CUGCCACCACCACCAUAGCNN 4282 NM_013842_27-45CUAUGGUGGUGGUGGCAGCNN 4217 GCUGCCACCACCACCAUAGNN 4218 NM_013842_732-750CUUACCAGCCUCCCUUUCUNN 3417 AGAAAGGGAGGCUGGUAAGNN 3418 Gene XBP-1reference transcript NM_013842 (Mus musculis XPB1 mRNA, FIG. 3) Notes100 siRNA sequences common to both mouse and rhesus

TABLE 13 XBP-1 mouse/Rhesus analysis of siRNAs off target mouse Anti-Anti- rhesus sense sense Sense Sense Antisense Antisense Sense SenseOligo Name Count Score Count Score Count Score Count ScoreNM_013842_369-387 4 3.2 2 2 1 2.8 1 2.4 NM_013842_237-255 3 3 1 2 2 2.214 1 NM_013842_491-509 1 3 1 2 1 2 5 2.2 NM_013842_917-935 9 3 1 2 1 2 52 NM_013842_923-941 7 3 2 1 1 1 1 1 NM_013842_702-720 2 2.8 8 2 4 2 1 2NM_013842_926-944 2 2.8 1 1 1 2 3 2 NM_013842_391-409 2 2.4 7 3 1 2 1 2NM_013842_775-793 2 2.4 5 2 3 2 2 2 NM_013842_1150-1168 3 2.2 1 2 1 2.81 2 NM_013842_776-794 3 2.2 6 2 1 2 1 1 NM_013842_921-939 1 2.2 1 2 2 24 2 NM_013842_777-795 6 2.2 3 2 1 1.2 4 2 NM_013842_539-557 2 2.2 4 2 51 4 2.2 NM_013842_731-749 3 2.2 4 2.8 1 1 1 1 NM_013842_924-942 2 2.2 32 1 1 1 2 NM_013842_1151-1169 1 2 1 2.2 2 3 1 1.2 NM_013842_1152-1170 12 1 2 2 3 2 2.2 NM_013842_1718-1736 1 2 5 3 20 3 1 2.2 NM_013842_368-3861 2 2 2 1 3 1 2.2 NM_013842_489-507 1 2 1 2 3 3 4 3 NM_013842_238-256 12 10 3 1 2.4 2 1 NM_013842_240-258 1 2 4 2 1 2.4 10 2 NM_013842_390-4082 2 18 3 4 2.2 1 1 NM_013842_487-505 1 2 3 2 1 2.2 5 2 NM_013842_741-7593 2 2 1 1 2.2 2 1.2 NM_013842_918-936 1 2 1 2 2 2.2 5 2NM_013842_919-937 2 2 2 2 3 2.2 1 1 NM_013842_1130-1148 1 2 2 2 12 2 1 1NM_013842_1712-1730 4 2 1 2 10 2 1 2.2 NM_013842_1714-1732 2 2 1 2 1 2 21 NM_013842_1717-1735 4 2 6 3 2 2 1 2.2 NM_013842_1719-1737 1 2 1 2 13 22 2 NM_013842_1775-1793 2 2 4 2 2 2 9 2 NM_013842_1776-1794 1 2 4 2 4 21 1 NM_013842_239-257 9 2 3 2 1 2 2 1 NM_013842_347-365 2 2 3 2 1 2 1 1NM_013842_348-366 3 2 5 2.2 1 2 1 1 NM_013842_485-503 2 2 1 2.2 13 2 3 2NM_013842_486-504 2 2 1 2 11 2 2 2 NM_013842_488-506 5 2 5 3 2 2 2 2NM_013842_540-558 6 2 4 2 2 2 1 2 NM_013842_703-721 2 2 8 2 7 2 3 2.2NM_013842_705-723 6 2 5 2.8 5 2 1 3 NM_013842_730-748 2 2 1 2.8 2 2 12.8 NM_013842_742-760 3 2 1 1 2 2 5 2 NM_013842_744-762 3 2 1 1 21 2 9 2NM_013842_767-785 6 2 6 2.2 7 2 3 2 NM_013842_771-789 7 2 3 1 11 2 5 2NM_013842_916-934 1 2 4 2.2 6 2 4 2 NM_013842_920-938 1 2 3 2 4 2 3 2NM_013842_922-940 3 2 2 1 1 2 2 2.2 NM_013842_925-943 1 2 1 2 2 2 1 1NM_013842_1720-1738 1 2 1 2.2 4 1 1 3 NM_013842_232-250 7 2 1 1 3 1 1 2NM_013842_236-254 1 2 2 2 2 1 1 1 NM_013842_728-746 22 2 2 2 6 1 1 2NM_013842_729-747 13 2 1 2.2 3 1 1 2.2 NM_013842_745-763 4 2 2 1 20 1 11 NM_013842_766-784 2 2 8 2 1 1 2 1 NM_013842_927-945 2 2 5 2 1 1 1 1NM_013842_234-252 6 2 1 1 1 0 2 1 NM_013842_235-253 2 2 1 1 1 0 1 1NM_013842_346-364 2 2 1 1 1 0 3 2 NM_013842_490-508 1 1.2 12 3 6 3 3 2NM_013842_700-718 1 1.2 3 2.2 4 3 2 2 NM_013842_1715-1733 1 1.2 6 3 3 21 1 NM_013842_734-752 1 1.2 1 1 7 2 5 2 NM_013842_773-791 2 1.2 1 2 1 21 2.2 NM_013842_778-796 1 1.2 3 2 7 2 2 2 NM_013842_779-797 1 1.2 5 3 12 1 2 NM_013842_1774-1792 1 1.2 1 1 1 1 4 2 NM_013842_704-722 2 1.2 1 24 1 1 2.2 NM_013842_1716-1734 1 1 5 3 9 3 1 1 NM_013842_1713-1731 1 1 12.2 3 2.2 2 2 NM_013842_768-786 1 1 2 2.2 2 2.2 4 2 NM_013842_1129-11471 1 2 2 1 2 1 1 NM_013842_389-407 1 1 2 2 1 2 3 2 NM_013842_701-719 2 11 1 4 2 4 2 NM_013842_706-724 3 1 6 2 1 2 1 3 NM_013842_707-725 2 1 1 13 2 1 3 NM_013842_727-745 1 1 1 2 1 2 1 2.2 NM_013842_733-751 2 1 1 2.22 2 3 2 NM_013842_736-754 1 1 3 2 3 2 6 1 NM_013842_738-756 2 1 7 2 7 23 1 NM_013842_743-761 1 1 2 2 4 2 2 2 NM_013842_769-787 1 1 2 2 8 2 2 0NM_013842_772-790 3 1 4 2 1 2 2 2 NM_013842_774-792 2 1 2 2 4 2 10 2NM_013842_231-249 2 1 1 1.2 1 1 2 2 NM_013842_233-251 4 1 4 2 2 1 2 2NM_013842_735-753 3 1 2 1 1 1 4 2 NM_013842_737-755 4 1 3 2 1 1 7 2NM_013842_739-757 2 1 6 2 4 1 1 1 NM_013842_740-758 1 1 9 2 1 1 1 1NM_013842_746-764 2 1 1 1 20 1 8 2 NM_013842_770-788 2 1 4 1 1 1 3 1NM_013842_26-44 4 1 1 1 15 1 9 1 NM_013842_27-45 2 1 2 2 10 1 1 1NM_013842_732-750 1 0 2 2.8 5 2 1 1 Gene XBP-1 reference transcriptNM_013842 (Mus musculis XPB1 mRNA, FIG. 3) Notes 100 siRNA sequencescommon to both mouse and rhesus

Other embodiments are in the claims.

We claim:
 1. A method of inhibiting XBP-1 expression in a cell, themethod comprising: (a) introducing into the cell a double stranded RNA(dsRNA), wherein said dsRNA comprises a sense strand and an antisensestrand that together form a region of complementarity less than 30 basepairs in length, and wherein said sense strand and said antisense strandare each less than 30 nucleotides in length, and wherein said antisensestrand is complementary to at least 15 contiguous nucleotides ofCACCCUGAAUUCAUUGUCU (SEQ ID NO: 2149); and (b) maintaining the cellproduced in step (a) for a time sufficient to obtain degradation of themRNA transcript of an XBP-1 gene, thereby inhibiting expression of theXBP-1 gene in the cell.
 2. The method of claim 1, wherein said antisensestrand or said sense strand comprises at least one modified nucleotide.3. The method of claim 2, wherein at least one of said modifiednucleotides is chosen from the group of: a 2′-O-methyl modifiednucleotide, a nucleotide comprising a 5′-phosphorothioate group, and aterminal nucleotide linked to a cholesteryl derivative, vitamin E, ordodecanoic acid bisdecylamide group.
 4. The method of claim 2, whereinsaid modified nucleotide is chosen from the group of: a2′-deoxy-2′-fluoro modified nucleotide, a 2′-deoxy-modified nucleotide,a locked nucleotide, an abasic nucleotide, 2′-amino-modified nucleotide,2′-alkyl-modified nucleotide, morpholino nucleotide, a phosphoramidate,and a non-natural base comprising nucleotide.
 5. The method of claim 1,wherein said antisense strand comprises SEQ ID NO:
 2150. 6. The methodof claim 1, wherein said sense strand comprises SEQ ID NO:
 2149. 7. Themethod of claim 1, wherein said antisense strand consists of SEQ ID NO:2150.
 8. The method of claim 1, wherein said sense strand consists ofSEQ ID NO:
 2149. 9. The method of claim 1, wherein said antisense strandcomprises SEQ ID NO: 2178 (AGAcAAUGAAUUcAGGGUGdTsdT).
 10. The method ofclaim 1, wherein said sense strand comprises SEQ ID NO: 2177(cAcccuGAAuucAuuGucudTsdT).
 11. The method of claim 1, wherein saidantisense strand consists of SEQ ID NO:
 2178. 12. The method of claim 1,wherein said sense strand consists of SEQ ID NO:
 2177. 13. The method ofclaim 1, wherein said antisense strand consists of SEQ ID NO: 2178 andsaid sense strand consists of SEQ ID NO:
 2177. 14. The method of claim1, wherein introducing said dsRNA into said cell inhibits expression ofthe XBP-1 gene by at least 40% compared to a level of XBP-1 geneexpression prior to contact of said cell with said dsRNA.
 15. The methodof claim 1, wherein said cell is a cancer cell.
 16. A method ofdecreasing XBP-1 expression in a liver of an animal and decreasingplasma cholesterol levels in said animal, comprising administering adouble stranded RNA (dsRNA) to said animal, wherein said dsRNA comprisesa sense strand and an antisense strand that together form a region ofcomplementarity less than 30 base pairs in length, and wherein saidsense strand and said antisense strand are each less than 30 nucleotidesin length, and wherein said antisense strand is complementary to atleast 15 contiguous nucleotides of CACCCUGAAUUCAUUGUCU (SEQ ID NO:2149).
 17. The method of claim 16, wherein said antisense strandcomprises SEQ ID NO:
 2150. 18. The method of claim 16, wherein saidsense strand comprises SEQ ID NO:
 2149. 19. The method of claim 16,wherein said human has cancer, a metabolic disease, a cardiovasculardisease, or a neurological disease.
 20. The method of claim 16, whereinadministering comprises administration by injection.
 21. The method ofclaim 20, wherein said injection is intravenous, intraarterial,subcutaneous, intraperitoneal or intramuscular injection.
 22. The methodof claim 16, wherein said animal is a mouse.
 23. The method of claim 16,wherein said animal is a human.